3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin

We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML

Cultivares de batata para sistemas orgânicos de produção.

Informações a respeito de cultivares adaptadas ao sistema de cultivo orgânico são escassas. O objetivo deste estudo foi avaliar, sob sistema de cultivo orgânico, genótipos nacionais e estrangeiros desenvolvidos para o cultivo convencional, quanto ao potencial produtivo, em condições de campo. O experimento foi conduzido em 2008, no Pólo APTA Leste Paulista, em Monte Alegre do Sul-SP. O delineamento experimental foi em blocos ao acaso, com 18 tratamentos e quatro repetições. Cada parcela foi constituída por 80 batatas-semente, dispostas em quatro linhas de 5 m de comprimento, espaçadas de 80 cm, com 25 cm entre tubérculos. Os genótipos avaliados foram Agata, Asterix, Caesar, Cupido, Éden, Melody, Novella e Vivaldi, de origem estrangeira; e Apuã, Aracy, Catucha, IAC Aracy Ruiva, Itararé, Monte Alegre 172, IAC 6090, APTA 16.5, APTA 15.20 e APTA 21.54, nacionais. Foram avaliadas as características de produtividade total e comercial de tubérculos, massa média total e comercial de tubérculos, teor de matéria seca e severidade da pinta-preta (Alternaria solani). Os clones APTA 16.5, APTA 21.54 e IAC 6090, e as cultivares Cupido, Apuã, Itararé e Monte Alegre 172 foram os mais produtivos. ‘APTA 21.54’ superou os demais em relação a produtividade comercial (18,07 t ha-1), sendo que ‘APTA 16.5’, ‘Cupido’, ‘IAC 6090’ e ‘Itararé’ formaram o segundo grupo. As maiores massas médias de tubérculos foram apresentadas pelas cultivares Itararé e Cupido. O clone IAC 6090 e as cultivares Aracy e Aracy Ruiva foram as que apresentaram maiores teores de matéria seca, com valor médio de 22,91%. ‘APTA 16.5’, ‘Apuã’, ‘Aracy’, ‘Aracy Ruiva’, ‘Éden’, ‘Ibituaçú’ e ‘Monte Alegre 172’ apresentaram alto nível de resistência à pinta-preta. As cultivares Itararé, Apuã e Cupido são adaptadas ao cultivo orgânico, e os clones avançados APTA 16.5, APTA 21.54 e IAC 6090 apresentam potencial de cultivo no sistema orgânico

Research itineraries: contribution to the knowledge of African migrations and afro-descendants in Argentina

In this chapter, we propose to present the paths walked as aresearch team since 1990, when we formed a heterogeneous anddiverse group in terms of age, gender, personality and academictraining, today called the Research Group on African Migrationsand Afro‐descendants in Argentina (GIMAAA). Intellectuallyand affectively involved in our work, a fruitful atmosphere wascreated for brainstorming, giving rise to a context of reciprocityfrom the passion that joined us ‐ research into migratory groupslocated in the province of Buenos Aires. Our physical workspacewas established in the Migratory Movements section of theEthnography Division of the Museum of Natural Sciences of LaPlata National University (UNLP). In the early stages of our work,much of the focus was on sourcing funding to enable us to carryout the research. In the following sections, we will outline theperiodization of the work carried out, taking account of thestudy?s central axes and the theoretical‐methodological approachdeveloped by the groupFacultad de Humanidades y Ciencias de la EducaciónFacultad de Ciencias Naturales y Muse

Proteomic expression profile of injured rat peripheral nerves revealed biological networks and processes associated with nerve regeneration

International audiencePeripheral nerve regeneration is regulated through the coordinated spatio-temporal activation of multiple cellular pathways. In this work, an integrated proteomics and bioinformatics approach was employed to identify differentially expressed proteins at the injury-site of rat sciatic nerve at 20 days after damage. By a label-free liquid chromatography mass-spectrometry (LC-MS/MS) approach, we identified 201 differentially proteins that were assigned to specific canonical and disease and function pathways. These include proteins involved in cytoskeleton signaling and remodeling, acute phase response, and cellular metabolism. Metabolic proteins were significantly modulated after nerve injury to support a specific metabolic demand. In particular, we identified a group of proteins involved in lipid uptake and lipid storage metabolism. Immunofluorescent staining for acyl-CoA diacylglycerol acyltransferase 1 (DGAT1) and DAGT2 expression provided evidence for the expression and localization of these two isoforms in Schwann cells at the injury site in the sciatic nerve. This further supports a specific local regulation of lipid metabolism in peripheral nerve after damage

Afroamérica : historia, cultura e identidad

Universidad Nacional Autónoma de México/Programa de Apoyo a Proyectos de Investigación e Innovación/"PAPIIT IN 402610"//[Estudios Afroamericanos. Aportes africanos a las culturas de nuestra América]Afroamérica es el nombre que se le ha dado "al conjunto de regiones y comunidades que tienen raíz africana", producto de un "proceso de traslado masivo y forzado de millones de hombres, mujeres y niños que desde su llegada, a partir del siglo XVI, conformaron parte de la población americana". Los estudios sobre estas regiones y comunidades se han venido desarrollando a pesar de enfrentar múltiples dificultades y en los años recientes han experimentado en nuestra América un vigoroso impulso, en gran medida, provocado por la acción cada vez más consciente y militante de los afrodescendientes latinoamericanos. Estos trabajos, originalmente presentados como ponencias en el Segundo Coloquio Afroamérica. Historia, cultura y procesos identitarios, fueron seleccionados por su valor académico ya que aportan al conocimiento de los estudios afroamericanos un rico y variado conjunto de elementos sobre temas poco conocidos relativos a las diversas expresiones culturales de los afrodescendientes de diferentes países de nuestra América. Estos aportes abarcan un universo que no se restringe a un determinado orden teórico o metodológico, ni a un solo enfoque o perspectiva, sino a una diversidad de posturas, algunas de ellas muy novedosas dentro de las tendencias actuales de las ciencias sociales y las humanidades. Los diversos debates de las últimas tres o cuatro décadas sobre la diversidad cultural, étnica y racial de nuestros pueblos en las esferas de lo social, lo económico y lo político constituyen el rico y variado contexto en el que se inscriben las investigaciones que han dado origen a los estudios que aquí presentamos.Libro

Some properties of the intestinal proteases of the rabbitfish, Siganus canaliculatus (Park)

10.1007/BF00004312Fish Physiology and Biochemistry143215-221FPBI

Myeloid differentiation primary response protein 88 blockade upregulates indoleamine 2,3-dioxygenase expression in rheumatoid synovial fibroblasts

Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-α, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity had higher levels of expression of IDO, TLR3 and TLR4 in the synovium than patients with mild disease activity. These data suggest that upregulation of IDO expression in synovial fibroblasts involves TLR3 and TLR4 activation by microbial constituents. We showed that the mechanisms responsible for IDO regulation primarily involve MyD88 signaling in synovial fibroblasts, as demonstrated by siRNA-mediated knockdown of MyD88

Laser scanning cytometry: understanding the immune system in situ

Flow cytometry allows quantitative analysis of the identity and effector function of individual cells. However, it cannot provide information on cellular responses that occur within physiological tissue microenvironments. Laser scanning cytometry is an emerging technology that allows imaging and quantitative analysis of individual cells in tissues in situ. This article describes the technology and its potential for delineating the molecular and cellular events underpinning the immune response in health and disease