Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

Colorectal cancer (CRC) is a disease whose genesis may include metabolic dysregulation. Cancer stem cells are attractive targets for therapeutic interventions since their aberrant expansion may underlie tumor initiation, progression, and recurrence. To investigate the actions of metabolic regulators on cancer stem cell-like cells (CSC) in CRC, we determined the effects of soybean-derived bioactive molecules and the anti-diabetes drug metformin (MET), alone and together, on the growth, survival, and frequency of CSC in human HCT116 cells. Effects of MET (60 μM) and soybean components genistein (Gen, 2 μM), lunasin (Lun, 2 μM), β-conglycinin (β-con, 3 μM), and glycinin (Gly, 3 μM) on HCT116 cell proliferation, apoptosis, and mRNA/protein expression and on the frequency of the CSC CD133(+)CD44(+) subpopulation by colonosphere assay and fluorescence-activated cell sorting/flow cytometry were evaluated. MET, Gen, and Lun, individually and together, inhibited HCT116 viability and colonosphere formation and, conversely, enhanced HCT116 apoptosis. Reductions in frequency of the CSC CD133(+)CD44(+) subpopulation with MET, Gen, and Lun were found to be associated with increased PTEN and reduced FASN expression. In cells under a hyperinsulinemic state mimicking metabolic dysregulation and without and with added PTEN-specific inhibitor SF1670, colonosphere formation and frequency of the CD133(+)CD44(+) subpopulation were decreased by MET, Lun and Gen, alone and when combined. Moreover, MET + Lun + Gen co-treatment increased the pro-apoptotic and CD133(+)CD44(+)-inhibitory efficacy of 5-fluorouracil under hyperinsulinemic conditions. Results identify molecular networks shared by MET and bioavailable soy food components, which potentially may be harnessed to increase drug efficacy in diabetic and non-diabetic patients with CRC.

Thiophenecarboxamide derivatives activated by EthA kill mycobacterium tuberculosis by inhibiting the CTP synthetase PyrG

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Extraocular Muscles in Patients With Infantile Nystagmus Adaptations at the Effector Level

Objective: To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods: Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results: In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions: The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control.

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS. Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (Invest Ophthalmol Vis Sci. 2012;53:7904-7911) DOI:10.1167/iovs.12-10283

CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death

CD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o- cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-kappaB and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase- and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.

[Colección de fotografías de Ayora] [Material gráfico]

[1-3]. Vistas panorámicas de Ayora (3 fot.) -- [4-6]. Vicenta Alarte Gómez, esposa de Juan Roglá Garrido, con vestido blanco con puntilla o con toquilla en el patio de la casa de Ayora, con palanganas, cepillo, tinaja, leña y también con macetas con flores (3 fot.) -- [7]. Vista general de la calle de la Marquesa en Ayora con carros y gente (1 fot.) -- [8]. Retrato de Facundo Roglá Alarte, Arcipreste de Torrent (1 fot.) -- [9] Facundo Rogla Alarte, sacerdote, en el huerto del patio de la casa (1 fot.) -- [10-11]. Retratos de grupo familiar de los Roglá Alarte junto a sacerdotes, entre ellos Facundo Roglá Alarte, en el patio de la casa con macetas con flores y parra (2 fot.) -- [12]. 8 retratos de José Roglá Alarte y miembros de su familia (1 fot.) -- [13]. Retrato de grupo familiar de los López Blat: Rosalia López Blat, con camisa rayada y toquilla, a sus derecha su madre; el niño de la izquierda es Francisco Roglá López con su hermana Amparo; la niña de arriba es Rosalia Roglá López (1 fot.) -- [14]. 8 retratos de Rosalia López Blat y miembros de su familia (1 fot.) -- [15]. Amparo y Rosalia Roglá López, 1900 (1 fot.) -- [16]. Pregonero tocando la corneta junto a labrador y niños con cántaro en la calle Empedrá de Ayora frente al número 20, casa de la familia Lliberós Roglá, la primera a la izquierda (1 par estereoscópico) (1 fot.) -- [17]. Entrada al pueblo de Ayora por la calle Mercadal con gente (1 fot.) -- [18-19]. El niño Francisco Roglá López en una casa de campo y con un cazador, 1900 (2 fot.) -- [20]. Casa de campo (1 par estereoscópico) (1 fot.) -- [21]. Grupo familiar comiendo una paella en la Ermita de la Virgen del Rosario de Ayora (1 fot.) -- [22]. Francisco Roglá López con su madre, hermanas y familia en el monte junto a un mojón con una bandera blanca (1 fot.) -- [23]. Rosalia López Blat con sus hijos, su hermana Carmen y familia en la montaña junto a un mojón con la inscripción: "vedado de caza", 1900 (1 fot.) -- [24]. El niño Francisco Roglá López con sombrero a la derecha de la imagen y Facundo Roglá Alarte el segundo por la derecha del grupo de sacerdotes (entre ellos José del Campo? y Afrusino?) en Ontinyent (1 fot.) -- [25]. El niño Francisco Roglá López con sombrero a la derecha de la imagen y Facundo Roglá Alarte el tercero por la derecha del grupo de sacerdotes (entre ellos José del Campo? y Afrusino?) en Ontinyent (1 fot.) -- [26]. Desfile de grupo de personas acompañando a un sacerdote, muchos de ellos con paraguas (1 fot.) -- [27]. José Roglá López con amigos o familiares modelando barro en la alfarería y fábrica de tejas y ladrillos los Torneros de Ayora (1 fot.) -- [28]. Alfarera pintando una vasija de cerámica en la fábrica los Torneros (1 par estereoscópico) (1 fot.)

KAT1 is not essential for stomatal opening

It is generally accepted that K+ uptake into guard cells via inward-rectifying K+ channels is required for stomatal opening. To test whether the guard cell K+ channel KAT1 is essential for stomatal opening, a knockout mutant, KAT1∷En-1, was isolated from an En-1 mutagenized Arabidopsis thaliana population. Stomatal action and K+ uptake, however, were not impaired in KAT1-deficient plants. Reverse transcription–PCR experiments with isolated guard cell protoplasts showed that in addition to KAT1, the K+ channels AKT1, AKT2/3, AtKC1, and KAT2 were expressed in this cell type. In impalement measurements, intact guard cells exhibited inward-rectifying K+ currents across the plasma membrane of both wild-type and KAT1∷En-1 plants. This study demonstrates that multiple K+ channel transcripts exist in guard cells and that KAT1 is not essential for stomatal action.

Variationen für das Piano-Forte /

Mode of access: Internet.

Index to United States documents relating to foreign affairs, 1828-1861 ...

Mode of access: Internet.

Freywillig-auffgesprungener Granat-Apffel dess christlichen Samaritans. Oder: Auss christlicher Lieb dess Nächsten eröffnete Gehaimbnuss vieler vortrefflichen sonders-bewährten Mitteln und wunder-heylsamen Artzneyen ... auss vieler Artzney-Erfahrner und berühmter Leib-Artzten oder Medicin-Doctorn lang-gepflogener Erfahrenheit ... zusammen getragen. Auffs neue vermehrt (sambt einer kleinen Diæta, wie sich bey jeder Kranckheit im Essen und Trincken zu verhalten; wie auch beygefügten neuen Koch-Buch in welchem allerhand räre und denen Patienten zu verschiedenen Kranckheiten erspriessliche Speisen) ...

Mode of access: Internet.

“Currículo encarnado”: cartografia simbólica e afinidades pós-coloniais

This thesis has as main objective to reflect about the defining conceptual elements of the embodied curriculum concept, ident ified curriculum conception from the analysis about the rationality employed in the doctoral work of teacher Antonio Fernando Gouvê a da Silva, entitled The construction of the curriculum in popular critical perspective: the significant words to the context ualized practices , written and defended in the Postgraduate Program in Education: Curriculum, in the Pontifícia Catholic University of São Paulo, in 2004. We looked, also, on the problematization of the affinities between postcolonial theories – analytical perspectives towards the discussion about coloniality and their effect on contemporary social weaving – and the embodied curriculum concept. We argue that the reflections present in the aforementioned work bring an articulated curriculum concept based on three conceptual symbiotic elements, namely: negativity, dialogue and praxis, which, by endorsing the possibility of a curricular ingrained practice in the life context of the individuals, have some post - colonial inclinations that lead to the problematizat ion about the neo - colonial manifestations in curricular sphere, outlining a critique of the modus operandi of the colonialism, particularly, in its cultural and epistemic dimension from which the education is inseparable. For that, we used as methodologica l procedure the symbolic cartography, knowledge building strategy systematized by Boaventura de Sousa Santos, which allowed us to construct interpretive maps that enabled the symbolization of the universe which we longed to understand, that is, the concept ual categories mentioned above, which, in our view, underlie the concept of embodied curriculum. In this direction, we anchored ourselves in a meaningful dialogue with the theoretical approach of Paulo Freire and some of his interpreters regarding the disc ussion on curriculum, especially the reflections dev eloped by Antonio Fernando Gouvê a da Silva, and authors whose theoretical developments resonate in prospects for humanization, social justice and empowerment, among which we highlight: Theodor Adorno, Hug o Zemelman, Wilfred Carr, Adolfo Sánchez Vázquez, among others. We seek, in the same manner, on the contributions of authors considered post - colonial, as Hugo Achugar, Gayatri Spivak, Boaventura de Sousa Santos and Enrique Dussel, to name a few, the reason s why we consider the embodied curriculum as a place of political - pedagogical enunciation, conducive to an educational praxis that engages in a curricular work of reality translation in order to see what overwhelms it to, then, elicit the construction of a school curriculum as an awareness project for releasing in relation to what is unjust and inhumane. We consider, finally, that the success of this curriculum embodied translation implies a larger number of speakers mobilized in the production of knowledge that yearns for social emancipation and contribute to the enrichment of human capabilities as the maintenance of the life and the dignity of people.

Uma escola e muitos sentidos: um estudo com os sujeitos jovens da EJA na Escola Estadual 15 de Outubro

Work that aims to understand the meanings attributed to school knowledge by young students of the EJA State School 15 October, located in the Natal’s North Zone. Young people were elected as the focus of interest for having a numerical expression increased in groups of adult education EJA, but above all, they demand for new issues and specific to school. For the research, we used methodologically the Comprehensive Interview organized by Kaufmann (2013), making use of its own analytical and organization of information, captured through semi-structured interviews and on-site observation. Whereas the meaning ascribed to it in relation to the school knowledge conditions the way to experience the school, sought the theoretical constructions of Bernard Charlot (2000; 2005), the understanding of knowledge as a relation of the subject with you, with each other and with the world, so we know beyond the object content. Analytical work incorporates also the contributions of Marc Augé (1994, 1997) with respect to the understanding of meaning as a social construction. Reflections were also made in light of Michel de Certeau (2012), in that it allows you to take the students as active subjects and producers of survival tactics in life and at school. From the speech of students, seized three units of meaning, namely: the learning considered most important by young students, which make up a set of ethical and moral values; the school as a guarantee of "a better future", in which young people seek to ensure a job in adulthood, however, from a "magical relationship" with knowledge, in that the target of young students is more the certificate completion of the level of education they attend, which is not necessarily associated with school learning. The third core seized sense is the school as a place of socialization, that is, a space where you can meet with friends to talk. There is therefore a relationship with knowledge that is prestigious for the youth of adult education EJA; there is an objective expectation of these students about the school; and they do "use" of the institution to "meetings" that are not necessarily with the curricular knowledge. Consider, therefore, these questions which hold school sense of reframing, is part of an effort to understand the subject of adult education EJA and helps to think ways to ensure continuity and their success in the institution.