iEndocr Relat Cancer, Vol. 11, No. 3. (September 2004), pp. 497-522./ibr /br /It is widely believed that ductal breast cancer dissemination involves a succession of clinical and pathological stages starting with carcinoma in situ, progressing into invasive lesion and culminating in metastatic disease. Such changes have frequently been attributed to the sequential acquisition of various alterations in a single cell followed by clonal selection and expansion, thus leading to intra-tumor diversity. According to this multi-step view, extensive genotype and phenotype (marker expression, grade) shift may occur in the same tumor during progression; this may lead to the co-existence of molecularly and/or pathologically different areas within the same lesion. An increasing amount of data of various natures now appear to challenge this concept: only a few distinct 'portraits', in relation to estrogen receptor (ER) status and grade, may be found among tumors. Moreover, although undergoing increasing genetic alteration, most individual lesions largely maintain their phenotype when they evolve from in situ to the metastatic state. While many of the data presented here are related to ductal tumors, lobular cancer is also discussed.br /iM Lacroix, RA Toillon, G Leclercq/i

Researchers from the European Molecular Biology Laboratory have developed a novel microscopy technique to generate "digital embryos," 3D visualizations of early embryonic development down to the position of individual cells and the division of those cells. Their first big success, published recently in the journal Science, is a reconstruction of the first 24 hours of a Zebrafish embryo's development. The resulting movies are quite spectacular. From an EMBL press release: Two newly developed technologies were key to the scientists' interdisciplinary approach to tracking a living zebrafish embryo from the single cell stage to 20,000 cells: a Digital Scanned Laser Light Sheet Microscope that scans a living organism with a sheet of light along many different directions so that the computer can assemble a complete 3D image, and a large-scale computing pipeline operated at the Karlsruhe Institute of Technology... "The digital embryo is like Google Earth for embryonic development. It gives an overview of everything that happens in the first 24 hours and allows you to zoom in on all cellular and even subcellular details," says Jochen Wittbrodt, who has recently moved from EMBL to the University of Heidelberg and the Karlsruhe Institute of Technology. The Zebrafish digital embryo(European Molecular Biology Laboratory), "Digital zebrafish embryo" press release (EMBL), "Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy" (Science, thanks Mark Pescovitz!)...br style="clear: both;"/ a href="http://www.pheedo.com/click.phdo?s=d88c46ba0965f5205c82098e25c6545cp=1"img alt="" style="border: 0;" border="0" src="http://www.pheedo.com/img.phdo?s=d88c46ba0965f5205c82098e25c6545cp=1"//a img src="http://www.pheedo.com/feeds/tracker.php?i=d88c46ba0965f5205c82098e25c6545c" style="display: none;" border="0" height="1" width="1" alt=""/

pFor all the magnificent diversity of life on this planet, ranging from tiny bacteria to majestic blue whales, from sunshine-harvshy;shy;estshy;shy;ing plants to mineral-digesting endoliths miles underground, only one kind of ldquo;life as we know itrdquo; exists. All these organisms are based on nucleic acids--DNA and RNA--and proteins, working together more or less as described by the so-called central dogma of molecular biology: DNA stores information that is transcribed into RNA, which then serves as a template for producing a protein. The proteins, in turn, serve as important structural elements in tissues and, as enzymes, are the cellrsquo;s workhorses./ppYet scientists dream of synthesizing life that is utterly alien to this world--both to better understand the minimum components required for life (as part of the quest to uncover the essence of life and how life originated on earth) and, frankly, to see if they can do it. That is, they hope to put together a novel combination of molecules that can self-organize, metabolize (make use of an energy source), grow, reproduce and evolve./p a href=http://www.sciam.com/article.cfm?id=triple-helix-designing-a-new-molecule[More]/a

An anonymous reader writes "James Boyle has released his new book, The Public Domain: Enclosing the Commons of the Mind (Yale University Prses) under a Creative Commons License. It can be downloaded free or read online. There are chapters on Thomas Jefferson's views of IP, musical borrowing and the birth of soul, free software, and synthetic biology. Lessig is impressed. Doctorow says he is a law prof who writes like a comedian (is this a good thing?), and credits Boyle's first book for getting him involved in online rights."pa href="http://yro.slashdot.org/article.pl?sid=08/11/30/2236247amp;from=rss"img src="http://slashdot.org/slashdot-it.pl?from=rssamp;op=imageamp;style=h0amp;sid=08/11/30/2236247"/a/ppa href="http://yro.slashdot.org/article.pl?sid=08/11/30/2236247amp;from=rss"Read more of this story/a at Slashdot./p pa href="http://feedads.googleadservices.com/~at/mykTjBi5fZzHEDQa4Z3zkHgCuzQ/a"img src="http://feedads.googleadservices.com/~at/mykTjBi5fZzHEDQa4Z3zkHgCuzQ/i" border="0" ismap="true"/img/a/pimg src="http://feedproxy.google.com/~r/Slashdot/slashdot/~4/p4iRYPEuKf8" height="1" width="1"/

iAdvances in experimental medicine and biology, Vol. 630 (2008), pp. 52-56./ibr /br /Breast cancer originates in undifferentiated terminal structures of the mammary gland. The terminal ducts of the Lob 1 of the human female breast, which are the sites of origin of ductal carcinomas, are at their peak of cell replication during early adulthood, a period during which the breast is more susceptible to carcinogenesis. The susceptibility of Lob 1 to undergo neoplastic transformation has been confirmed by in vitro studies, which have shown that this structure has the highest proliferative activity, estrogen receptor content and rate of carcinogen binding to the DNA. The higher incidence of breast cancer observed in nulliparous women supports this concept, whereas the protection afforded by early full-term pregnancy in women could be explained by the higher degree of differentiation of the mammary gland at the time in which an etiologic agent or agents act.br /iJ Russo, IH Russo/i

iBreast Cancer Research and Treatment, Vol. 108, No. 3. (1 April 2008), pp. 351-361./ibr /br /Abstract  The estrogen receptor (ER) is the single most powerful predictor of breast cancer prognosis as well as an important contributor to the biology of carcinogenesis. In addition, endocrine therapy targeting ER directly (SERMS) or indirectly (aromatase inhibitors) forms the mainstay of adjuant therapy. Traditionally, human tumors are scored for the amount and presence of ER. However, this has centered on the population of ER found in the transformed epithelial cell nucleus. Over the last 40 years, it has been appreciated that additional cellular ER pools exist, in cytoplasm and at the plasma membrane. In this review, we discuss the important functions of extra-nuclear ER in breast cancer, including integration of function with nuclear ER.br /iEllis Levin, Richard Pietras/i

iAdvances in experimental medicine and biology, Vol. 630 (2008), pp. 189-205./ibr /br /Loss of normal growth control is a hallmark of cancer. Thus, understanding the mechanisms of tissue-specific, normal growth regulation and the changes that occur during tumorigenesis may provide insights of both diagnostic and therapeutic importance. Control of cell proliferation in the normal mammary gland is steroid hormone (estrogen and progestin)-dependent, involves complex interactions with other hormones, growth factors and cytokines and ultimately converges on activation of three proto-oncogenes (c-Myc, cyclin D1 and cyclin E1) that are rate limiting for the G1 to S phase transition during normal cell cycle progression. Mammary epithelial cell-specific overexpression of these genes induces mammary carcinoma in mice, while cyclin D1 null mice have arrested mammary gland development and are resistant to carcinoma induced by the neu/erbB2 and ras oncogenes. Furthermore, c-Myc, cyclins D1, E1 and E2 are commonly overexpressed in primary breast cancer where elevated expression is often associated with a more aggressive disease phenotype and an adverse patient outcome. This may be due in part to overexpression of these genes conferring resistance to endocrine therapies since in vitro studies provide compelling evidence that overexpression of c-Myc and to a lesser extent cyclin D1 and cyclin E1, attenuate the growth inhibitory effects of SERMS, antiestrogens and progestins in breast cancer cells. Thus, abnormal regulation of the expression of cell cycle molecules, involved in the steroidal control of cell proliferation in the mammary gland, are likely to be directly involved in the development, progression and therapeutic responsiveness of breast cancer. Furthermore, a more detailed understanding of these pathways may identify new targets for therapeutic intervention particularly in endocrine-unresponsive and endocrine-resistant disease.br /iAJ Butt, CE Caldon, CM McNeil, A Swarbrick, EA Musgrove, RL Sutherland/i

Out of the jaws of death: PRMT5 steers p53

Nature Cell Biology 10, 1389 (2008). doi:10.1038/ncb1208-1389

Author: Shelley L. Berger

The tumour suppressor p53 triggers either cell-cycle arrest or apoptosis. Now, arginine methylation joins a panoply of other post-translational modifications that regulate p53. PRMT5 mediates p53 methylation, which disposes the cell to arrest rather than death.

Under arrest in mitosis: Cdc20 dies twice

Nature Cell Biology 10, 1385 (2008). doi:10.1038/ncb1208-1385

Authors: Andrew M. Fry & Hiroyuki Yamano

The spindle assembly checkpoint is crucial for maintaining genome integrity in dividing cells by preventing premature chromosome segregation. Degradation of the APC/C activator Cdc20 seems to be an essential and conserved mechanism to maintain this checkpoint in the presence of chromosomes that are not attached to the mitotic spindle.

iThe International Journal of Biochemistry & Cell Biology, Vol. 39, No. 7-8. ( 2007), pp. 1329-1336./ibr /br /This article explores the impact of new insights in the biology of cancer on the treatment and the prevention of this disease. There are two types of targeted cancer treatment, afforded by the molecular profile of cancer. One concerns the use of agents targeted on a specific component of the cancer cells (e.g., CD20 in lymphoma) or on a specific survival function of the cancer cell (growth-factor-receptor interaction; transduction cascade). The other concerns the recognition of tumors that are more or less likely to benefit from cytotoxic chemotherapy according to their genomic or proteomic profile. Cancer prevention may benefit from new molecular insight in cancer biology as these processes allow early diagnosis of cancer, identification of patients at risk for cancer, and may provide intermediate markers for chemoprevention studies.br /iLodovico Balducci/i

Cuban MD with Masters in Biochemistry and several literary publications, including essays, short stories and one novel.br / br / Available to tutor the following subjects: Biology, Chemistry, World History and Economics.br / br / Experienced teacher with a passion for knowledge; has abandoned a scientific career in favour of a literary one.br / br / Will customize the tutoring program to the individual student, and meet students at their home, at a public library or another suggested location.br / br / For more information, please call 514-510-5515.br /

A model for transmission of the H3K27me3 epigenetic mark

Nature Cell Biology 10, 1484 (2008). doi:10.1038/ncb1208-1484

Authors: Klaus H. Hansen, Adrian P. Bracken, Diego Pasini, Nikolaj Dietrich, Simmi S. Gehani, Astrid Monrad, Juri Rappsilber, Mads Lerdrup & Kristian Helin

Exploring the pole: an EMBO conference on centrosomes and spindle pole bodies

Nature Cell Biology 10, 1375 (2008). doi:10.1038/ncb1208-1375

Authors: Sue L. Jaspersen & Tim Stearns

iJournal of Mammary Gland Biology and Neoplasia/ibr /br /Abstract  Epidemiologic studies demonstrate that breast cancer is the most common type of cancer diagnosed in women and is a significant cause of morbidity and mortality. While there are many risk factors known to be associated with increased breast cancer risk, this review will focus specifically on circulating IGF-I, hyperinsulinemia, and type 2 diabetes. Their effects on promoting breast cancer development, progression, and adverse outcomes have been demonstrated in both animal and human studies, suggesting that the IGF system is a potential target for breast cancer therapy. In addition, in the clinical setting, emphasizing metabolic risk modifications to patients including weight loss, dietary changes, and diabetes control may also play an important role in breast cancer risk reduction.br /iDanielle Lann, Derek Leroith/i

Do the protocadherins Fat and Dachsous link up to determine both planar cell polarity and the dimensions of organs?

Nature Cell Biology 10, 1379 (2008). doi:10.1038/ncb1208-1379

Authors: Peter A. Lawrence, Gary Struhl & José Casal

Research highlights

Nature Cell Biology 10, 1391 (2008). doi:10.1038/ncb1208-1391

Authors: Nathalie Le Bot, Bernd Pulverer, Christina Karlsson Rosenthal & Sowmya Swaminathan

A TRP channel-steroid marriage

Nature Cell Biology 10, 1383 (2008). doi:10.1038/ncb1208-1383

Authors: Bernd Nilius & Thomas Voets

A surprising functional association between TRPM3, a mysterious member of the family of transient receptor potential (TRP) cation channels, and the sulphated version of pregnenolone, 'mother' of all steroid hormones, has been identified.

iBulletin of Mathematical Biology, Vol. 5, No. 4. (21 December 1943), pp. 115-133./ibr /br /Abstract  Because of the “all-or-none” character of nervous activity, neural events and the relations among them can be treated by means of propositional logic. It is found that the behavior of every net can be described in these terms, with the addition of more complicated logical means for nets containing circles; and that for any logical expression satisfying certain conditions, one can find a net behaving in the fashion it describes. It is shown that many particular choices among possible neurophysiological assumptions are equivalent, in the sense that for every net behaving under one assumption, there exists another net which behaves under the other and gives the same results, although perhaps not in the same time. Various applications of the calculus are discussed.br /iWarren Mcculloch, Walter Pitts/i

George Palade 1912–2008

Nature Cell Biology 10, 1374 (2008). doi:10.1038/ncb1208-1374

Author: David D. Sabatini

Staying alive: apoptosome feedback inhibition

Nature Cell Biology 10, 1387 (2008). doi:10.1038/ncb1208-1387

Author: Hermann Steller

Studies in Drosophila melanogaster reveal a mechanism for regulating caspases, the key executioners of the apoptotic cell-death program. An initiator caspase and its activating partner promote degradation of each other, thereby limiting the levels of the active protease complex. This negative-feedback inhibition helps to explain how cells avoid unwanted caspase activation and apoptosis.

Italy fails to nurture knowledge

Nature Cell Biology 10, 1373 (2008). doi:10.1038/ncb1208-1373

Silvio Berlusconi's government seems set on its course to reform Italy's troubled education system through heavy cuts in funding to schools, universities and scientific research, prompting a belated flurry of protests.

Publication Date: 2008 Nov 27 PMID: 19038985br/Authors: Mukherjee, S. - Pelech, S. - Neve, R. M. - Kuo, W. L. - Ziyad, S. - Spellman, P. T. - Gray, J. W. - Speed, T. P.br/Journal: Bioinformaticsbr/br/MOTIVATION: Combinatorial effects, in which several variables jointly influence an output or reponse, play an important role in biological systems. In many settings, Boolean functions provide a natural way to describe such influences. However, biochemical data using which we may wish to characterize such influences are usually subject to much variability. Furthermore, in high-throughput biological settings Boolean relationships of interest are very often sparse, in the sense of being embedded in an overall dataset of higher dimensionality. This motivates a need for statistical methods capable of making inferences regarding Boolean functions under conditions of noise and sparsity. RESULTS: We put forward a statistical model for sparse, noisy Boolean functions and methods for inference under the model. We focus on the case in which the form of the underlying Boolean function, as well as the number and identity of its inputs are all unknown. We present results on synthetic data and on a study of signalling proteins in cancer biology. AVAILABILITY: go.warwick.ac.uk/sachmukherjee/sci. CONTACT: S.N.Mukherjee@warwick.ac.uk.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038985title=Entrez+PubmedCiteULike/a