Biology

In 2008, doctor Sergio Canavero, an italian neurosurgeon based in Turin, IT, have awakened a 20 years old lady from a permanent post-traumatic vegetative state, by means of a bifocal extradural cortical electro-stimulation. Today, while Science still find it hard to explain consciousness and embodied cognition – the world-class neurosurgeon made a shock announcement: “I’m ready for the first head transplant on a man.” In the manuscript published on Surgical Neurology International, he reveals the details of this astonishing project, named HEAVEN. Including ethical questions.... Canavero, S. (2013) HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surgical Neurology International, 4(2), 335. DOI: 10.4103/2152-7806.113444 HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI)

The study of how cells move in development is not just about development. Understanding cell migration can also help researchers understand how tumors spread and invade other tissues. So, the next time you see someone roll their eyes at your fruit fly egg chambers (or worm vulva, or culture dishes), take pity at their ignorance and explain to them how they should thank you instead.The movement of cells during development drives the shape changes and organization of an embryo. In the fruit fly ovary, a small cluster of border cells migrates across a region of the egg chamber in order to reach the oocyte. This collective migration of these border cells depends on polarization of the actin cytoskeleton. A recent paper describes the role of the Hippo signaling pathway in driving the polarization of actin to the outer rim of the migrating border cell cluster. Lucas and colleagues found that upstream Hippo pathway components localize to the contacts between border cells within the cluster in order to link polarity signaling with actin cytoskeleton organization. In the images above, the actin cytoskeleton (red) can be seen at the outer rim of the migrating cluster of border cells (arrows) as it moves across the egg chamber towards the oocyte (top to bottom, chronologically). Higher magnification views of the cluster are on the right. Lucas, E., Khanal, I., Gaspar, P., Fletcher, G., Polesello, C., Tapon, N., & Thompson, B. (2013). The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells originally published in the Journal of Cell Biology, 201 (6), 875-885 DOI: 10.1083/jcb.201210073... Lucas, E., Khanal, I., Gaspar, P., Fletcher, G., Polesello, C., Tapon, N., & Thompson, B. (2013) The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells. originally published in the Journal of Cell Biology, 201(6), 875-885. DOI: 10.1083/jcb.201210073 The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells

There is a really interesting article at Slate.Com from Mary Ann Mason, the author of "Do Babies Matter" which I have written about here before. The post is titled "In the Ivory Tower, Men Only". The post tells some of the background behind the book and discusses issues about graduate school, post doctoral positions, applying for faculty jobs and more. The article also has some very good guidance for universities that would like to level the playing field: We all know what structural changes would help to level the playing field in all of these careers and they are quite similar: paid family leave for both mothers and fathers, especially for childbirth, a flexible workplace, a flexible career track, a re-entry policy, pay equity reviews, child care assistance, dual career assistance. Those universities and corporations who have actively created these policies have found an advantage in recruitment and retention. For instance, at Berkeley, after enacting several new policies to benefit parents, including paid teaching leaves for fathers, job satisfaction scored much higher among parents, and more babies are being born to assistant professors. Some good guidance for some of the activities at UC Davis as part of the ADVANCE program in which I am involved. And she ends by recommending It is time for women to “lean in” and demand family policies that will at least give them a fighting chance to have both a successful career and babies. I agree. But it is also time for men to do the same. The more that men also support and demand such policies the quicker things will change. -------- This is from the "Tree of Life Blog" of Jonathan Eisen, an evolutionary biologist and Open Access advocate at the University of California, Davis. For short updates, follow me on Twitter. --------

After what seemed like an eternity, the epic saga known as AMP v. Myriad Genetics has finally come to a close. On June 13, 2013, the Supreme Court ruled (1) that isolated genomic DNA (gDNA) is not patent-eligible under section 101 of the Patent Act, but (2) cDNA is. For once, what the Justices said at oral argument gave accurate clues to what they really thought, and the result was what almost every observer (including this one) had predicted. The opinion—by Justice Thomas—was unanimous and brief: 18 pages. Justice Scalia wrote a one-paragraph concurrence in which he said only that he didn’t know enough to sign on to the Court’s recitation of “the details of molecular biology,” though he agreed with the decision. The 9-0 decision reflects a recent trend in patent decisions (see Mayo v. Prometheus and last month’s Monsanto opinion), and may represent a reaction to the derision that greeted the fractured, multi-opinion mess that was Bilski v. Kappos, the Court’s 2010 business methods case. Beyond the surface unanimity, the Myriad opinion has a no-brainer quality—that is, the opinion does not give any sense of wrestling with a difficult issue, giving the impression that the outcome was so clear that reasonable minds couldn’t possibly differ. Consistent with this approach, the Court cited only the lower court opinions and briefs in the case, a few of its own patent decisions, and a single scientific text (Watson’s Molecular Biology of the Gene). No amicus briefs (except the government’s, to confirm that the Department of Justice had thrown the USPTO under the bus), no scientific or law review articles. The strict legal significance of the decision is pretty straightforward. The Court struck down patent claims on genomic DNA that has been merely “isolated” from the body, where “isolated” means, well, “isolated”—removed and separated from its natural environment in the cell. More specifically, the Court held that genomic DNA does not meet the threshold test of patentable subject matter under section 101. It upheld the subject matter status of cDNA, which it defined as “synthetically created DNA . . . which contains the same protein-coding information found in a segment of natural DNA but omits portions within the DNA segment that do not code for proteins [introns].” Every patent drafted like Myriad’s first and broadest claim—“an isolated DNA coding for [a specified protein]”—is now invalid. Conversely, claims limited to cDNA versions of genes continue to pass the threshold test, though they are still subject to scrutiny under all the other patentability requirements (more on that below). The cDNA/gDNA distinction has its roots in the Federal Circuit’s 1991 decision in Amgen v. Chugai. That case turned on a priority-of-invention contest: who got the rights to the human EPO gene. But the case did, at least implicitly, establish the subject matter status of cDNA. The broadest claim upheld in that case was: “A purified and isolated DNA sequence consisting essentially of a DNA sequence encoding human erythropoietin.” The court treated this as a claim to the cDNA version of the gene, interpreting “purified” as meaning something like “only the coding regions.” It commented that “[i]t is important to recognize that [neither competing inventor] invented EPO or the EPO gene. The subject matter [of this claim] was the novel purified and isolated sequence which codes for EPO.” Thereafter, two things happened. First, the subject matter eligibility of cDNA was never again challenged, until now. And understandably so, if DNA is viewed as a chemical for patent law purposes. cDNA is, in a literal sense, a substance not found in the body; it contains the same coding information as the mature RNA transcript, but it is a different chemical: and, with the noncoding regions excised, it is not exactly replicated in natural DNA. The second thing was less predictable. Amgen set up one of those slippery slopes that lawyers are always talking about. The USPTO

Pesticide levels considered environmentally friendly in Europe and Australia are, in fact, having a devastating effect on invertebrate insect biodiversity in nearby creeks and streams, a new study has found, showing the need for an urgent overhaul of the way pesticide risk is assessed. Water-dwelling invertebrates like worms, snails, crustaceans, mites and insects play a crucial role in regional ecosystems because they provide food for fish, birds and platypuses.... Beketov, M., Kefford, B., Schafer, R., & Liess, M. (2013) Pesticides reduce regional biodiversity of stream invertebrates. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1305618110 Pesticides reduce regional biodiversity of stream invertebrates

I announced in an earlier post the realisation of the Repository of Ontologies for MULtiple USes ROMULUS foundational ontology library as part of Zubeida’s MSc thesis, as well as that a very brief overview describing it was accepted as a poster/demo paper [1] at the 7th International Conference on Knowledge Capture (KCAP’13) that will take place next week in Banff, Canada. The ‘sneak preview’ of the poster in jpeg format is included below. To stay in style, it has roughly the same colour scheme as the ontology library. The poster’s content is slightly updated compared to the contents of the 2-page poster/demo paper: it has more detail on the results obtained with the automated alignments. On reason for that is the limited space of the KCAP paper, another is that a more comprehensive evaluation has been carried out in the meantime. We report on those results in a paper [2] recently accepted at the 5th International Conference on Knowledge Engineering and Ontology Development (KEOD’13). The results of the tools aren’t great when compared to the ‘gold standard’ of manual alignments and mappings, but there are some interesting differences due to—and thanks to—the differences in the algorithms that the tools use. Mere string matching generates false positives and misses ‘semantic [near-]synonyms’ (e.g., site vs. situoid, but missing perdurant/occurrent), and a high reliance on structural similarity causes a tool to miss alignments (compare, e.g., the first subclasses in GFO vs. those in DOLCE). One feature that surely helps to weed out false positives is the cross-check whether an alignment would be logically consistent or not, as LogMap does. That is also what Zubeida did with the complete set of alignments between DOLCE, BFO, and GFO, aided by HermiT and Protégé’s explanation feature. The KEOD paper describes those ‘trials and tribulations’; or: there are many equivalence alignments that do not map due to a logical inconsistency. They have been analysed on the root cause (mainly: disjointness axioms between higher-level classes), and, where possible, solutions are proposed, such as subsumption instead of equivalence or proposing to make them sibling classes. Two such examples of alignments that do not map are shown graphically in the poster: a faltering temporal region that apparently means something different in each of the ontologies, and necessary-for does not map to generic-dependent due to conflicting domain/range axioms. The full list of alignments, mappings, and logical inconsistencies is now not only browsable on ROMULUS, as announced in the KCAP demo paper, but also searchable. Having said that, it is probably worthwhile repeating the same caution made in the paper and previous blog post: what should be done with the inconsistencies is a separate issue, but at least now it is known in detail where the matching problems really are, so that we can go to the next level. And some mappings are possible, so some foundational ontology interchangeability is possible (at least from a practical engineering viewpoint). References [1] Khan, Z.C., Keet, C.M. Toward semantic interoperability with aligned foundational ontologies in ROMULUS. Seventh International Conference on Knowledge Capture (K-CAP’13), ACM proceedings. 23-26 June 2013, Banff, Canada. (poster &demo) [2] Khan, Z.C., Keet, C.M. Addressing issues in foundational ontology mediation. Fifth International Conference on Knowledge Engineering and Ontology Development (KEOD’13). 19-22 September, Vilamoura, Portugal.

For half the population, it comes three to five days each month, 12 months each year, for 40 years of our lives. Menstruation can be debilitating, relieving, disappointing, or simply an inconvenient fact of life. But why do humans menstruate, when most animals don’t? When you shake the tree of life, you find that only a handful of mammals aside from us – primates, a small number of bat species, and the elephant shrew – have opted for the monthly bleed.... Emera, D., Romero, R., & Wagner, G. (2012) The evolution of menstruation: A new model for genetic assimilation. BioEssays, 34(1), 26-35. DOI: 10.1002/bies.201100099 The evolution of menstruation: A new model for genetic assimilation Blanks, A., & Brosens, J. (2013) Meaningful menstruation. BioEssays, 35(5), 412-412. DOI: 10.1002/bies.201300022 Meaningful menstruation

File under “interesting articles that I don’t have time to write about at length.” Archaea and Fungi of the Human Gut Microbiome: Correlations with Diet and Bacterial Residents Long ago, before metagenomics and NGS, I did a little work on detection of Archaea in human microbiomes. There’s a blog post in the pipeline about that but until then, enjoy this article in PLoS ONE. Mutational heterogeneity in cancer and the search for new cancer-associated genes This article is getting a lot of attention on Twitter this week. Brief summary: cancer cells are really messed up in all sorts of ways, most of which are not causal with respect to the cancer. Anyone who has ever looked at microarray data knows that it’s not uncommon for 50% or more of genes to show differential expression in a cancer/normal comparison, so this is hardly a new concept. I think we need to move away from ever-more detailed characterizations of the ways in which cancer cells are “messed up.” We know that they are and that doesn’t provide much insight, in my opinion. The vast majority of statistical analysis is not performed by statisticians Interesting post by Jeff Leek, summarized very well by its title. It points out that many more people are now interested in data analysis, many of them are not trained professionally as statisticians (I’m in this category myself) and we need to recognize and plan for that. Bonus post doing the rounds of social media: Using Metadata to Find Paul Revere. Social network analysis, 18th-century style. Amusing, informative and topical. Filed under: publications, statistics Tagged: archaea, cancer, microbiology, statistics

Researchers have analysed the genome sequences of Mycobacterium leprae samples from the teeth and bones of mediaeval skeletons. ? M. leprae is the bacillus that causes leprosy, which was endemic in Europe until mediaeval times; whilst cases have dropped world-wide, it persists in regions outs ...

Unanimous decision against BRCA breast cancer susceptibility gene patents in Association for Molecular Pathology v. Myriad Genetics, Inc. Plus: a movie about BRCA1 discoverer Mary-Claire King.... Hall, J., Lee, M., Newman, B., Morrow, J., Anderson, L., Huey, B., & King, M. (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science, 250(4988), 1684-1689. DOI: 10.1126/science.2270482 Linkage of early-onset familial breast cancer to chromosome 17q21 Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L., Ding, W.... (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science, 266(5182), 66-71. DOI: 10.1126/science.7545954 A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 Wooster, R., Neuhausen, S., Mangion, J., Quirk, Y., Ford, D., Collins, N., Nguyen, K., Seal, S., Tran, T., Averill, D.... (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science, 265(5181), 2088-2090. DOI: 10.1126/science.8091231 Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13