NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice.

NIH/3T3 cells transfected with DNA from malignant human tumors produced experimental and spontaneous metastases in nude mice. In contrast, parent or spontaneously transformed NIH/3T3 cells failed to metastasize. The transfected clones contained either activated c-Harvey-ras or N-ras oncogenes. A representative clone (T71-17SA2) which was used to assess selected cellular and host factors relevant to the metastatic process produced lung metastases in 100% of the NIH nude mice recipients, secreted augmented levels of type IV collagenase, and invaded human amnion basement membrane in vitro. Expression of the metastatic phenotype was not related to decreased sensitivity to natural killer cells or macrophage-mediated cytotoxicity. Analysis of the cellular DNA from the T71-17SA2 transfectant and its corresponding metastases, both of which contained activated N-ras oncogenes, revealed a twofold increase in the N-ras-specific DNA sequences in the metastatic cells. Thus, transfection with human tumor DNA containing activated ras oncogenes can induce the complete metastatic phenotype in NIH/3T3 cells by a mechanism apparently unrelated to immune cell killing.     

Book reviews

Stephen Cornell, THE RETURN OF THE NATIVE: AMERICAN INDIAN POLITICAL RESURGENCE, New York and Oxford: Oxford University Press, 1988, 278 pp., $29.95.

Jack D. Forbes, BLACK AFRICANS AND NATIVE AMERICANS: COLOR, RACE AND CASTE IN THE EVOLUTION OF RED‐BLACK PEOPLES, Oxford and New York: Basil Blackwell, 1988, 334 pp., £35.00.

Maryon McDonald, ’WE ARE NOT FRENCH!’: LANGUAGE, CULTURE AND IDENTITY IN BRITTANY, London: Routledge, 1989, 384 pp., £40.00.

Ronald Grigor Suny, THE MAKING OF THE GEORGIAN NATION, London: I. B. Taurus and Co. Ltd., 1989, ix‐395 pp., £29.50.

Shlomo Deshen, THE MELLAH SOCIETY: JEWISH COMMUNITY LIFE IN SHERIFIAN MOROCCO, translated and revised from the Hebrew by the author. Chicago: The University of Chicago Press, 1989, xii + 152 pp., £23.95 and £9.50 (paper).

Roger Waldinger, Howard Aldrich, Robin Ward and Associates, ETHNIC ENTREPRENEURS: IMMIGRANT BUSINESS IN INDUSTRIAL SOCIETIES, Sage Series on Race and Ethnic Relations, vol. 1., Newbury Park, CA: Sage Publications, 1990, 226 pp., £29.25 and £13.95 (paper).

Saul Dubow, RACIAL SEGREGATION AND THE ORIGINS OF APARTHEID IN SOUTH AFRICA, 1919–36, St Antony's and Macmillan, London, 1989, xi and 250 pp., £35.00.

Mark Duffield, BLACK RADICALISM AND THE POLITICS OF DE‐INDUSTRIALISATION: THE HIDDEN HISTORY OF INDIAN FOUNDRY WORKERS, Avebury, 1988, 226 pp., £24.50.

John Eade, THE POLITICS OF COMMUNITY: THE BANGLADESHI COMMUNITY IN EAST LONDON, Avebury, 1989, 213 pp., £24.00.

Nicole Hahn Rafter (ed.), WHITE TRASH: THE EUGENICS FAMILY STUDIES 1877–1919, Boston: Northeastern University Press, 1988, 382 pp., £36.00.

Neil R. McMillen, DARK JOURNEY ‐ BLACK MISSISSIPPIANS IN THE AGE OF JIM CROW, Urbana, Ill: University of Illinois Press, 1989, N.P.L.     

Latitude drives diversification in Madagascar's endemic dry forest rodent Eliurus myoxinus (subfamily Nesomyinae)

Numerous hypotheses have been proposed for the historical processes governing the rich endemism of Madagascar's biodiversity. The ‘watershed model’ suggests that drier climates in the recent geological past have resulted in the contraction of forests around major watersheds, thereby defining areas of endemism. We test whether this hypothesis explains phylogeographical patterns in a dry forest‐dependent rodent, Eliurus myoxinus, an endemic species widely distributed through western Madagascar. We sequenced the mitochondrial cytochrome b locus and nuclear introns of the β‐fibrinogen and the growth hormone receptor genes for E. myoxinus. Using a parametric bootstrapping approach, we tested whether the mitochondrial gene tree data fit expectations of local differentiation given the watershed model. We additionally estimated population differentiation and historical demographic parameters, and reconstructed the spatial history of E. myoxinus to highlight spatial and temporal patterns of differentiation. The data do not support the watershed model as a clear explanation for the genetic patterns of diversity within extant E. myoxinus populations. We find striking patterns of latitudinal genetic structure within western Madagascar, and indicate possible roles for environmental and ecological gradients along this axis in generating phylogeographical diversity. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 110 , 500–517.     

M-1/M-2 macrophages and the Th1/Th2 paradigm

Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6, B10D2) are more easily activated to produce NO with either IFN-gamma or LPS than macrophages from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1, macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply describe activated or unactivated macrophages, but cells expressing distinct metabolic programs. Because NO inhibits cell division, while ornithine can stimulate cell division (via polyamines), these results also indicate that M-1 and M-2 responses can influence inflammatory reactions in opposite ways. Macrophage TGF-beta1, which inhibits inducible NO synthase and stimulates arginase, appears to play an important role in regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages cause CB6F1 lymphocytes to increase IFN-gamma production, while BALB/c SCID macrophages increase TGF-beta production. Together, the results indicate that M-1- or M-2-dominant macrophage responses can influence whether Th1/Th2 or other types of inflammatory responses occur.     

Structural Brain Changes after Traditional and Robot-Assisted Multi-Domain Cognitive Training in Community-Dwelling Healthy Elderly

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly.

Trial Registration

ClnicalTrials.gov NCT01596205     

Increased Blood Levels of Growth Factors,Proinflammatory Cytokines,and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th₁) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th₁₇ pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th₁₇ cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.     

Free-air exposure systems to scale up ozone research to mature trees

Because seedlings and mature trees do not necessarily respond similarly to O(3) stress, it is critically important that exposure systems be developed that allow exposure of seedlings through to mature trees. Here we describe three different O(3) Free-Air Exposure Systems that have been used successfully for exposure at all growth stages. These systems of spatially uniform O(3) release have been shown to provide reliable O(3) exposure with minimal, if any, impact on the microclimate. This methodology offers a welcome alternative to chamber studies which had severe space constraints precluding stand or community-level studies and substantial chamber effects on the microclimate and, hence physiological tree performance.     

Distribution Patterns of Isomorphic Cold-Water Dinoflagellates (Scrippsiella/Woloszynskia Complex) Causing ‘red tides’ in the Baltic Sea

During the latest years medium-sized (15–30 μm), single-celled dinoflagellates have been reported to form blooms in the northern Baltic Proper and the Gulf of Finland in winter and spring. Recent studies (Kremp et al., 2003. Proceedings of the 7th International conference of Modern and Fossil Dinoflagellates, September 21–25, Nagasaki, Japan, 66 pp.) indicate that those blooms are caused by two isomorphic species – Scrippsiella hangoei (Schiller) Larsen, and a new species, tentatively belonging to the genus Woloszynskia. Until now there has been no report on how widely distributed these phytoplankton species are in the Baltic Sea. In this study, the occurrence of Scrippsiella/Woloszynskia complex in the entire Baltic Sea was investigated, by using monitoring data from 1997 to 2003. The species occurred in a salinity range from 2 to 8 PSU. Highest concentrations were observed at salinity 4.5–6.5 PSU. Maximum cell densities of Scrippsiella/Woloszynskia complex in the water column were mainly obtained in April or in the beginning of May by the water temperature <3 °C prior to stratification was formed. In the central Gulf of Finland, the second maximum was found in 1999 and 2002 by the temperature >6 °C. Bloom formations in the Baltic Proper and in the Gulf of Finland may not only be explained by optimum temperature and salinity, but also with other factors e.g. high nutrient concentrations and good seeding conditions from the sediments.