Selections from the writings of Mary Jesup : late of Halstead, Essex : with some account of two of her children.

Mode of access: Internet.

Retinoic Acid-Treated Pluripotent Stem Cells Undergoing Neurogenesis Present Increased Aneuploidy and Micronuclei Formation

The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs) are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA) in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC) cells, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naive cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal variation accompanies neurogenesis in vitro.

The Snake Venom Peptide Bj-PRO-7a Is a M1 Muscarinic Acetylcholine Receptor Agonist

Proline-rich peptides from Bothrops jararaca venom (Bj-PRO) were characterized based on the capability to inhibit the somatic angiotensin-converting enzyme. The pharmacological action of these peptides resulted in the development of Captopril, one of the best examples of a target-driven drug discovery for treatment of hypertension. However, biochemical and biological properties of Bj-PROs were not completely elucidated yet, and many recent studies have suggested that their activity relies on angiotensin-converting enzyme-independent mechanisms. Here, we show that Bj-PRO-7a (DGPIPP) specifically activates [Ca(2+)](i) transients in CHO-M1 cells expressing heterologous rat M1 muscarinic subtype. The activation curve established by microfluorimetry in CHO-M1 cells using increasing concentrations of Bj-PRO-7a reached the maximum response in the presence of 3 mu M Bj-PRO-7a (EC(50) = 0.25 +/- 0.07 mu M). The variation observed by calcium imaging in these cells ranged from 52 to 1218 nM (EC(50) = 0.31 +/- 0.12 mu M). [Ca(2+)](i) responses in CHO-M1 cells were largely inhibited by pirenzepine, a specific M1 antagonist. Neural-differentiated P19 cells expressing endogenous M1 receptors were also responsive to Bj-PRO-7a application, whereas no such response was observed in undifferentiated P19 cells not expressing muscarinic receptors. As further support for its specific action on M1 receptors, the peptide did not activate M3 subtypes in transfected CHO cells. Our findings provide a novel M1 muscarinic receptor agonist that could be used for basic research and even for pharmacological applications. (C) 2010 International Society for Advancement of Cytometry

Directed Differentiation of Neural Progenitors into Neurons Is Accompanied by Altered Expression of P2X Purinergic Receptors

Neural differentiation has been extensively studied in vitro in a model termed neurospheres, which consists of aggregates of neural progenitor cells. Previous studies suggest that they have a great potential for the treatment of neurological disorders. One of the major challenges for scientists is to control cell fate and develop ideal culture conditions for neurosphere expansion in vitro, without altering their features. Similar to human neural progenitors, rat neurospheres cultured in the absence of epidermal and fibroblast growth factors for a short period increased the levels of beta-3 tubulin and decreased the expression of glial fibrillary acidic protein and nestin, compared to neurospheres cultured in the presence of these factors. In this work, we show that rat neurospheres cultured in suspension under mitogen-free condition presented significant higher expression of P2X2 and P2X6 receptor subunits, when compared to cells cultured in the presence of growth factors, suggesting a direct relationship between P2X2/6 receptor expression and induction of neuronal differentiation in mitogen-free cultured rat neurospheres.

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

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

Regulation of neurogenesis and gliogenesis of retinoic acid-induced P19 embryonal carcinoma cells by P2X2 and P2X7 receptors studied by RNA interference

Embryonic carcinoma cells are widely used models for studying the mechanisms of proliferation and differentiation occurring during early embryogenesis. We have now investigated how down-regulation of P2X2 and P2X7 receptor expression by RNA interference (RNAi) affects neural differentiation and phenotype specification of P19 embryonal carcinoma cells. Wild-type P19 embryonal carcinoma cells or cells stably expressing shRNAs targeting P2X2 or P2X7 receptor expression were induced to differentiate into neurons and glial cells in the presence of retinoic acid. Silencing of P2X2 receptor expression along differentiation promoted cell proliferation and an increase in the percentage of cells expressing glial-specific GFAP, while the presence of beta-3 tubulin-positive cells diminished at the same time. Proliferation induction in the presence of stable anti-P2X2 receptor RNAi points at a mechanism where glial proliferation is favored over growth arrest of progenitor cells which would allow neuronal maturation. Differently from the P2X2 receptor, inhibition of P2X7 receptor expression during neural differentiation of P19 cells resulted in a decrease in cell proliferation and GFAP expression, suggesting the need of functional P2X7 receptors for the progress of gliogenesis. The results obtained in this study indicate the importance of purinergic signaling for cell fate determination during neural differentiation, with P2X2 and P2X7 receptors promoting neurogenesis and gliogenesis, respectively. The shRNAs down-regulating P2X2 or P2X7 receptor gene expression, developed during this work, present useful tools for studying mechanisms of neural differentiation in other stem cell models. (C) 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Ice Core Paleovolcanic Records from the St. Elias Mountains, Yukon, Canada

We previously reported a record of regionally significant volcanic eruptions in the North Pacific using an ice core from Eclipse Icefield (St. Elias Mountains, Yukon, Canada). The acquisition of two new ice cores from Eclipse Icefield, along with the previously available Eclipse Icefield and Mount Logan Northwest Col ice cores, allows us to extend our record of North Pacific volcanism to 550 years before present using a suite of four ice cores spanning an elevation range of 3 - 5 km. Comparison of volcanic sulfate flux records demonstrates that the results are highly reproducible, especially for the largest eruptions such as Katmai ( A. D. 1912). Correlation of volcanic sulfate signals with historically documented eruptions indicates that at least one-third of the eruptions recorded in St. Elias ice cores are from Alaskan and Kamchatkan volcanoes. Although there are several moderately large ( volcanic explosivity index (VEI) >= 4) eruptions recorded in only one core from Eclipse Icefield, the use of multiple cores provides signals in at least one core from all known VEI >= 4 eruptions in Alaska and Kamchatka since A. D. 1829. Tephrochronological evidence from the Eclipse ice cores documents eruptions in Alaska (Westdahl, Redoubt, Trident, and Katmai), Kamchatka (Avachinsky, Kliuchevoskoi, and Ksudach), and Iceland (Hekla). Several unidentified tephra-bearing horizons, with available geochemical evidence suggesting Alaskan and Kamchatkan sources, were also found. We present a reconstruction of annual volcanic sulfate loading for the North Pacific troposphere based on our ice core data, and we provide a detailed assessment of the atmospheric and climatic effects of the Katmai eruption.

[Calligraphic specimen, 1206, i.e. 1791 or 1792].

Exquisite album of calligraphy (muraqqaʻ / murakkaa) employing ḥadīth of the Prophet executed by the celebrated Ottoman calligrapher Mahmud Celâleddin Efendi (d.1829) in imitation of a model executed by the master calligrapher Hafız Osman Efendi (d.1698).

Report of a trial : Miles Farmer, versus Dr. David Humphreys, Storer, commenced in the Court of common pleas, April term, 1830, from which it was appealed to the Supreme judicial court, and by consent of parties, referred to referees, relative to the transactions between Miss Eliza Dolph and George Washington Adams /

Action for libel.

The theatre of the Greeks, or, The history, literature, and criticism of the Grecian drama; with an original treatise on the principal tragic and comic metres.

"An introduction to the principal Greek tragic and comic metres in scansion, structure, and ictus; by James Tate": p. [455]-529.

The Irishman in London; or, The happy African. A farce. In two acts. Performed at the Theatre-Royal, Covent-Garden.

Error in paging: no. 32-37 repeated.

The Monthly review.

Mode of access: Internet.

Petite galerie historique, ornée de gravures.

Mode of access: Internet.

Verwandlungen,

Mode of access: Internet.