Farnesyltransferase inhibitors induce dramatic morphological changes of KNRK cells that are blocked by microtubule interfering agents

Farnesyltransferase inhibitors (FTIs) exhibit the remarkable ability to inhibit transformed phenotypes of a variety of human cancer cell lines and to block the growth of cancer cells in a number of animal model systems. In this paper, we report that the addition of FTI to v-K-ras- transformed NRK cells (KNRK) results in dramatic morphological changes. Within 24 h after the addition of FTI, the round morphology of KNRK cells was changed to an elongated (flattened and spread out) morphology resembling those of untransformed NRK cells. No morphological effects were seen when similar concentrations of FTI were added to NRK cells. Phalloidin staining showed that FTI treatment did not restore the disrupted actin cytoskeleton in KNRK cells. In contrast, FTI addition resulted in the appearance of extensive microtubule networks in KNRK cells. The addition of a low concentration (1.2 nM) of vincristine or vinblastine, agents that interfere with microtubule dynamics, blocked the FTI-induced morphological changes in KNRK cells. In contrast, cytochalasin B, which interferes with actin polymerization, did not block the morphological changes. The FTI-induced morphological changes were associated with a decrease in the percentage of cells in S-phase, and the addition of 1.2 nM vincristine did not have additional effects on cell cycle progression. A higher concentration (12 nM) of vincristine caused synergistic effect with FTI to enrich dramatically KNRK cells in G2/M phase. These results suggest that FTI affects cell morphology and that microtubule dynamics are involved in these processes.

Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility

Little is known about stem cell biology or the specialized environments or niches believed to control stem cell renewal and differentiation in self-renewing tissues of the body. Functional assays for stem cells are available only for hematopoiesis and spermatogenesis, and the microenvironment, or niche, for hematopoiesis is relatively inaccessible, making it difficult to analyze donor stem cell colonization events in recipients. In contrast, the recently developed spermatogonial stem cell assay system allows quantitation of individual colonization events, facilitating studies of stem cells and their associated microenvironment. By using this assay system, we found a 39-fold increase in male germ-line stem cells during development from birth to adult in the mouse. However, colony size or area of spermatogenesis generated by neonate and adult stem cells, 2–3 months after transplantation into adult tubules, was similar (∼0.5 mm2). In contrast, the microenvironment in the immature pup testis was 9.4 times better than adult testis in allowing colonization events, and the area colonized per donor stem cell, whether from adult or pup, was about 4.0 times larger in recipient pups than adults. These factors facilitated the restoration of fertility by donor stem cells transplanted to infertile pups. Thus, our results demonstrate that stem cells and their niches undergo dramatic changes in the postnatal testis, and the microenvironment of the pup testis provides a more hospitable environment for transplantation of male germ-line stem cells.

Negative frequency-dependent selection maintains a dramatic flower color polymorphism in the rewardless orchid Dactylorhiza sambucina (L.) Soò

The orchid Dactylorhiza sambucina shows a stable and dramatic flower-color polymorphism, with both yellow- and purple-flowered individuals present in natural populations throughout the range of the species in Europe. The evolutionary significance of flower-color polymorphisms found in many rewardless orchid species has been discussed at length, but the mechanisms responsible for their maintenance remain unclear. Laboratory experiments have suggested that behavioral responses by pollinators to lack of reward availability might result in a reproductive advantage for rare-color morphs. Consequently, we performed an experiment varying the relative frequency of the two color morphs of D. sambucina to test whether rare morph advantage acted in the natural habitat of the species. We show here clear evidence from this manipulative experiment that rare-color morphs have reproductive advantage through male and female components. This is the first demonstration, to our knowledge, that negative frequency-dependent selection through pollinator preference for rare morphs can cause the maintenance of a flower-color polymorphism.

A catalogue of books in the College library: [which Benjamin Welles wished to read], 1797

In this small paper-bound catalog, Benjamin Welles (1781-1860) listed books in the Harvard College Library which he wished to read. He presumably compiled the list by consulting the Library's 1790 printed catalog, as the works are categorized according to subjects outlined in that catalog (Antiquities, Astronomy, Ancient Authors, Biography, Sacred Criticism, Ethics, Geography, Geometry, History, Nature, Travels / Voyages, Natural Law, Logic, Metaphysics, Miscellaneous Works, Dramatic, Phililogy, Natural Philosophy, Poetry, Rhetoric, and Theology). The final pages of Welles' catalog, which he titles "Another Selection," list additional volumes he wished to read. These are listed alphabetically, A - G. Some titles throughout the catalog have been marked with a "+" perhaps to indicate that Welles had read them.

The EU’s Paradoxical Efforts at Tracking the Financing of Terrorism: From criticism to imitation of dataveillance. CEPS Paper in Liberty and Security No. 56, August 2013

In July 2011, the European Commission published a Communication aimed at setting out different options for establishing a European terrorist finance tracking system (TFTS). The Communication followed the adoption of the EU-US agreement on the US Terrorist Finance Tracking Program (TFTP) in 2010. The agreement concluded various series of national, European and transatlantic negotiations after the disclosure through public media of the US TFTP in 2006. This paper takes stock of the wide range of controversies surrounding this security-focused programme with dataveillance capabilities. After stressing the impact of the US TFTP on international relations, the paper argues that the EU-US agreement primarily has the effect of shifting information-sharing practices from the justice/judicial/penal/criminal investigation framework into the security/intelligence/administrative/prevention context as the main rationale. The paper then questions the TFTP-related conception of mass intelligence through large-scale databases and transnational communication of bulk data in the name of targeted surveillance. Following an examination of the project creating an EU system equivalent to the TFTP, the paper emphasises the fundamental paradox of transatlantic security matters, in which European criticism of American programmes tends to be ultimately translated into EU imitation of US dataveillance practices.

Euroscepticism vs. Political Pragmatism: The Finns Party tones down its criticism of the EU. EPIN Commentary No. 19, 26 June 2014

While many Eurosceptic parties in Europe achieved historical successes in this year’s EP elections, Finland’s populist Finns Party was unable to fulfil its own high expectations. With the eurozone crisis at least temporarily subsiding and Finland’s own economy struggling, the party has been unable to find a new electoral trump card. Facing a changed political climate and stiffer competition, the party is currently toning down its criticism of the EU, as indicated by its recent decision to join the British Tories in the European Conservatives and Reformists (ECR) group.

A study of the dramatic works of Thomas Heywood ...

Thesis (M.L.)--Univ. of California. May, 1897.

Old masters and new; essays in art criticism,

Reprinted from various periodicals.

The Danube; the dramatic history of the great river and the people touched by its flow.

Includes bibliography.

Federal centralization; a study and criticism of the expanding scope of congressional legislation,

Mode of access: Internet.