CDK9: A key player in cancer and other diseases Franco, Lia Carolina; Morales, Fátima; Boffo, Silvia ...
Journal of cellular biochemistry,
February 2018, Letnik:
119, Številka:
2
Journal Article
Recenzirano
Cyclin‐Dependent Kinase 9 (CDK9) is part of a functional diverse group of enzymes responsible for cell cycle control and progression. It associates mainly with Cyclin T1 and forms the Positive ...Transcription Elongation Factor b (p‐TEFb) complex responsible for regulation of transcription elongation and mRNA maturation. Recent studies have highlighted the importance of CDK9 in many relevant pathologic processes, like cancer, cardiovascular diseases, and viral replication. Herein we provide an overview of the different pathways in which CDK9 is directly and indirectly involved.
Cyclin‐Dependent Kinase 9 (CDK9) is part of a functional diverse group of enzymes responsible for cell cycle control and progression. Recent studies have highlighted the importance of CDK9 in many relevant pathologic processes, like cancer, cardiovascular diseases, and viral replication. Herein we provide an overview of the different pathways in which CDK9 is directly and indirectly involved.
Inflammation in the diabetic retina is mediated by leukocyte adhesion to the retinal vasculature and alteration of the blood-retinal barrier (BRB). We investigated the role of chemokines in the ...alteration of the BRB in diabetes. Animals were made diabetic by streptozotocin injection and analyzed for gene expression and monocyte/macrophage infiltration. The expression of CCL2 (chemokine ligand 2) was significantly up-regulated in the retinas of rats with 4 and 8 weeks of diabetes and also in human retinal endothelial cells treated with high glucose and glucose flux. Additionally, diabetes or intraocular injection of recombinant CCL2 resulted in increased expression of the macrophage marker, F4/80. Cell culture impedance sensing studies showed that purified CCL2 was unable to alter the integrity of the human retinal endothelial cell barrier, whereas monocyte conditioned medium resulted in significant reduction in cell resistance, suggesting the relevance of CCL2 in early immune cell recruitment for subsequent barrier alterations. Further, using Cx3cr1-GFP mice, we found that intraocular injection of CCL2 increased retinal GFP+ monocyte/macrophage infiltration. When these mice were made diabetic, increased infiltration of monocytes/macrophages was also present in retinal tissues. Diabetes and CCL2 injection also induced activation of retinal microglia in these animals. Quantification by flow cytometry demonstrated a two-fold increase of CX3CR1+/CD11b+ (monocyte/macrophage and microglia) cells in retinas of wildtype diabetic animals in comparison to control non-diabetic ones. Using CCL2 knockout (Ccl2-/-) mice, we show a significant reduction in retinal vascular leakage and monocyte infiltration following induction of diabetes indicating the importance of this chemokine in alteration of the BRB. Thus, CCL2 may be an important therapeutic target for the treatment of diabetic macular edema.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of pH (3.5, 5.3 and 7.0) on the formation of deacylated gellan gels was studied using oscillatory shear measurements and microcalorimetric trials in heating–cooling cycles at 1°Cmin−1. In ...addition, the mechanical properties and structure of the gels formed at the different pH values were evaluated by uniaxial compression and scanning electron microscopy, respectively. An increase in pH led to an increase in temperature and decrease in enthalpy of the coil–helix transition. These results were attributed to a decreased formation of junction zones at higher pH values due to greater electrostatic repulsion between the gellan molecules. As a consequence, gels formed at neutral pH were more fragile and deformable than acid gels. All the samples showed thermo-reversible rheological behavior, presenting the same rheological properties at 20°C, before and after heating to 90°C.
Betalains are plant pigments with biological properties and can be used instead of synthetic colorants to confer color and functional properties to foods. The objective of this work was to carry out ...the chemical characterization of two varieties of prickly pear of Opuntia ficus‐indica, one of yellow‐orange coloration (Mandarina) and the other of purple coloration (Vigor), through measurements of chemical parameters and color in pulp, antioxidant activity, total phenolic compounds, and betalain content. Considering the thermolability of betalains and their potential applications in food, the thermal stability and activation energy of betacyanins from Vigor variety and betaxanthins from the Mandarina variety were also evaluated and compared with those from beetroot, the main source of betalains. Results for chemical characterization agreed with previous prickly pear reports of other regions, while the thermal degradation kinetics of betalains showed a first‐order degradation pattern with respect to time and temperature treatment. Betacyanins from Vigor prickly pear showed similar thermal stability to those from beetroot, which was reflected in similar values of activation energy, while betaxanthins from Mandarina prickly pear showed a higher stability, and therefore a higher activation energy, than those from beetroot. Based on the results, the prickly pear varieties used in this study can be considered as a good source of betalains with potential applications in food and, in addition, the methodology for the evaluation of thermostability can be used to compare the stability of betalains from different sources in a temperature range of 50–90°C.
Practical Application
The varieties of prickly pear used in this study can be considered a good source of red‐purple and yellow‐orange easily extractable pigments. In addition, we report a methodology that can be used for the evaluation of the thermal stability of these pigments and to compare this stability between different plant sources. Gaining knowledge on betalain thermal stability will make it possible to propose specific applications, for example, in processed foods requiring different pigment stabilities.
El fotógrafo berlinés conocido como Helmut Newton, plasmó en su estilo denominado como porno chic un repertorio muy completo de objetos y escenarios fetiche.
The heme-based and CO-responsive RcoM transcriptional regulators from Burkholderia xenovorans are known to display an extremely high affinity for CO while being insensitive to O2. We have ...quantitatively characterized the heme–CO interaction in full-length RcoM-2 and compared it with the isolated heme domain RcoMH-2 to establish the origin of these characteristics. Whereas the CO binding rates are similar to those of other heme-based sensor proteins, the dissociation rates are two to three orders of magnitude lower. The latter property is tuned by the yield of CO escape from the heme pocket after disruption of the heme–CO bond, as determined by ultrafast spectroscopy. For the full-length protein this yield is ∼0.5%, and for the isolated heme domain it is even lower, associated with correspondingly faster CO rebinding kinetics, leading to K d values of 4 and 0.25 nM, respectively. These differences imply that the presence of the DNA-binding domain influences the ligand-binding properties of the heme domain, thus abolishing the observed quasi-irreversibility of CO binding to the isolated heme domain. RcoM-2 binds target DNA with high affinity (K d < 2 nM) when CO is bound to the heme, and the presence of DNA also influences the heme–CO rebinding kinetics. The functional implications of our findings are discussed.
Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and ...protozoan infections, malnutrition and anemia in school-age Venezuelan children.
This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism.
Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20).
In rural populations in Venezuela helminthiasis and giardiasis were associated with acute and chronic nutritional status respectively. These data highlight the need for an integrated approach to control transmission of parasites and improve the health status of rural Venezuelan children.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Em um contexto sociotécnico marcado por uma intensa disputa pela atenção, plataformas digitais investem em estratégias de formação de hábitos, uma vez que isso garantiria o retorno automático dos ...usuários. Neste artigo, discutiremos as relações entre as engrenagens do capitalismo de vigilância e da economia da atenção a partir de uma análise metodologica do modelo do gancho, guia prático de design comportamental que combina mecanismos psicológicos e tecnológicos voltados para formar hábitos. O gancho é entendido como exemplo emblemático do que chamamos de tecnobehaviorismo para designar a tecnociência que atualiza referências ao pensamento behaviorista, visando a construção de interações humano-computador através de princípios de condicionamento. Argumentaremos que, no elo indissociável entre capitalismo de vigilância e economia da atenção, o tecnobehaviorismo oferece modelos teóricos e práticos ideais para atingir os objetivos econômicos das plataformas digitais, visando o engajamento. Com um olhar crítico, concluímos que a formação tecnobehaviorista de hábito articula modos de automatizar a captura da atenção e o controle do comportamento, explorando vulnerabilidades humanas por mecanismos sutis de influência psicológica e um controle fino dos estímulos nas arquiteturas de escolha dos ambientes digitais.
A fundamental question in cell biology underlies how nutrients are regenerated to maintain and renew tissues. Physiologically, the canonical Wnt signaling is a vital pathway for cell growth, tissue ...remodeling, and organ formation; pathologically, Wnt signaling contributes to the development of myriad human diseases such as cancer. Despite being the focus of intense research, how Wnt intersects with the metabolic networks to promote tissue growth and remodeling has remained mysterious. Our understanding of metabolism has been revolutionized by technological advances in the fields of chemical biology, metabolomics, and live microscopy that have now made it possible to visualize and manipulate metabolism in living cells and tissues. The application of these toolsets to innovative model systems have propelled the Wnt field into new realms at the forefront answering the most pressing paradigms of cell metabolism in health and disease states. Elucidating the basis of Wnt signaling and metabolism in a cell-type and tissue-specific manner will provide a powerful base of knowledge for both basic biomedical fields and clinician scientists, and has the promise to generate new, transformative therapies in disease and even processes of aging.
Este trabajo aborda la polémica iniciada en 1990 desde el British Museum acerca de la legitimidad de tres pinjantes de perrillo de oro, esmaltados y aderezados con piedras preciosas, procedentes del ...Tesoro del Pilar de Zaragoza que, subastados públicamente en 1870, hoy se encuentran dispersos. Los tres pinjantes se han considerado por la historiografía falsificaciones realizadas hacia 1860; no obstante, la documentación de la Santa Capilla del Pilar demuestra que dos de ellos son genuinas obras del Renacimiento (ca. 1580-1600). Al menos dos falsificadores europeos copiaron piezas originales, lo que plantea la revisión de la historia de la orfebrería a partir de las obras que, con certeza, son legítimas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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