(in US dollars) asks Pimm – the partial immortalization blog. A first response to this question -based on Google adsense revenues- is about $0.47/post. I think that prices depend on context – from negative balance (wasted time) to a new research direction (+tenure +$100,000) there is everything possible.
The testimony of Francis Collins before the subcommittee on Health is now online
A recent NIH study of families at risk for hereditary nonpolyposis colorectal cancer … revealed that the number concern expressed by participants regarding genetic testing was about losing health insurance, should the knowledge of their genetic test result be divulged or fall into the “wrong hands” … Unless Americans are convinced that their genetic information will not be used against them, the era of personlized medicine may never come to pass. The rest would be a continuation of the current one-size-fits-all medicine, ignoring the abundant scientific evidence that the genetic differences among people help explain why some of us benefit from a therapy while others do not.
While optimizing the analysis strategy for a 500,000 SNP Affymetrix array set, I found 6 autosomal SNPs that show highly significant sex-dependent allele differences: rs2809868, rs4862188, rs2880301, rs3883011, rs3883013 and rs3883014.
Sure, there could be autosomal marker that influences male/female outcome but there is a more likely explanation: All SNPs have paralogue sequence stretches on the Y chromosome that are co-amplified during PCR. From the initial genotyping results it is most likely that only the Y chromosomal stretch is being mutated in SNP 4, 13 and 15.2.
These SNPs are perfect sex marker, as they include an autosomal control allele (in comparison to pure Y markers like SNPs in SRY). They are always unambiguous (in contrast to pure X marker where only heterocygotes are informative).
They even offer advantage to commercial STR kits of the Amelogenin/Amely gene situated (in the Y parautosomal region) as they would not be affected by excess homologous X chromosomal material as often found in forensic situations. In addition, they might overcome some other weakness of the Amelogenin test where a second assay is usually recommended.
If you will ever see a case-control study that is highlighting any of these SNPs, you can be sure that this study had a distorted male-female ratio between case and controls.
One of my favorite pictures is the Orangenesser by Baselitz – his speciality is to paint his subjects the other way around to free the subject from its content (this is at least what art curators say).
DNA inversion rearrangements seem to be also more frequent in the human genome as previously thought, see the following PNAS preprint:
Three such regions … on chromosomes 3, 15, and 19, were analyzed. … The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth.
A funny study in PNAS is broadening our view of paranormal inheritance by showing germline chimerism in marmosets:
Using microsatellite DNA markers, we show here that chimerism in marmoset (Callithrix kuhlii) twin … somatic tissue .. found to be chimeric. Notably, chimerism was demonstrated to be present in germ-line tissues, an event never before documented as naturally occurring in a primate. In fact, we found that chimeric marmosets often transmit sibling alleles acquired in utero to their own offspring.
Bad news for all who believe in human paternity testing and 99,999999% probability – and more strange stories (semi-identical twins discovered – hermaphrodite reveals previously unknown type of twinning) at the Nature news blog.
Sciencesque has noticed it first: T shirts at Biomed Central for sale. Do your really want that shirt?
As far as I know vitamin D3 influences only RUNX2 expression (RUNX2 has a VDRE, possibly also RUNX3 but not RUNX1?). The RUNX factors
colocalized in common subnuclear foci. Furthermore, RUNX subnuclear foci contain the co-regulatory protein CBFβ, which heterodimerizes with RUNX factors, and nascent transcripts as shown by BrUTP incorporation. These results suggest that RUNX subnuclear foci may represent sites of transcription containing multi-subunit transcription factor complexes.
Variants in RUNX1 have already been reported earlier to be weakly associated with IgE serum levels in Korea.
A Nature paper todays reports that Foxp3 controls Treg function by interacting with AML1/RUNX1 – is there any connecting path?
DirectShowSource (“c:\video\videofile.mov”)
Another German University carries his name, but his tombstone is here in Munich: Alter Südlichen Friedhof, Thalkirchner Str. 240, Eingang Kapuzinerstr., D-80469 München.
The New Yorker has the background details
Stephen is Joyce’s only living descendant, and since the mid-nineteen-eighties he has effectively controlled the Joyce estate. Scholars must ask his permission to quote sizable passages or to reproduce manuscript pages from those works of Joyce’s that remain under copyright—including “Ulysses†and “Finnegans Wakeâ€â€”as well as from more than three thousand letters and several dozen unpublished manuscript fragments…
Over the years, the relationship between Stephen Joyce and the Joyceans has gone from awkwardly symbiotic to plainly dysfunctional…
and the Lessig blog the results of the current controversy
As reported at the Stanford Center for Internet and Society, Shloss v. Estate of James Joyce has settled. As you can read in the settlement agreement, we got everything we were asking for, and more (the rights to republish the book). This is an important victory for a very strong soul, Carol Shloss, and for others in her field.
Public Rambling on copyright problems in science blogs
What I always feared, but couldn’t believe, is now confirmed by renowned experts in a new Cell editorial
Historically, the word “epigenetics” was used to describe events that could not be explained by genetic principles.
It goes back to Conrad Waddington – and describes now such bizarre and inexplicable features like paramutation in maize, position effetc variegation in Drosophila and methylation in humans. There is a nice analogy of the classical 1957 epigenetic landscape figure of Waddington where the course of the ball is influenced by hillls and valleys where it finally arrives – the Pinball arcade game
known factors that may regulate epigenetic phenomena are shown direcing the complex movements of pinballs (cells) across the elegant landscape … no specific order of molecular events is implied; as such a sequence remains unknown. Effector proteins recognize specific histone modifications…
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Also outside the genetics community many people wonder why Popper’s account of falsifiability has so readily be abandoned. Karl Popper used falsification in “Logic of Scientific Discovery” as a criterion of demarcation between what is and what is not genuinely scientific.
Paul K. Feyerabend, one of Poppers many famous scholars at the London School of Economics- defended in “Against Method” (Feyerabend 1993) the view that there are no methodological rules which can be always used by scientists. He objected to any single prescriptive scientific method (like falsification) as any such method would limit the activities of scientists, and restrict scientific progress. Progress instead occurs where new theories are not consistent with older theories; a new theory also can never be consistent with all relevant facts: this make falsification attempts useless. Feyerabend advocated in a rather anarchistic view that scientific pluralism improves the critical power of science and not any schematic rules like profile population x with SNP panel y and describe all p less than z to finally develop new treatment t.
Many reasons why genetic association studies failed have been already identified (see Buchanan et al. 2006). Usually high impact journals get spectacular claims first; half-way down between Popper and Feyerabend, the editorial board looks for falsifiability by claiming additional populations.
As expected, effect sizes will not be exactly the same in different populations; often only neighbouring SNP “rescue” the initial claim. It has never been decided by a formal process, what does it mean if a third or fourth population doesn’t show up with the same result. It has never been clarified that falsifiability means that the exactly same SNP needs to be associated in all population studies or just a haplotype (or just a microsatellite allele) somewhere in that genomic region.
Nevertheless replication validity – in the context of generalization – is permanently used to prove “true” or “meaningful” association that ultimately deserve a high impact factor. Humans look different and they seem different in genetic terms: the high individual variablity in expressing a disease trait may reflect not only reflect a highly variable environment but also highly individual genetic pathway. We are willing to accept a causal mutation found in just one family with a monogenic trait often there seems no way to convince an editorial board that a strong association found in just one study sample is an important discovery that may severely impact exactly this population (given additional functional proof of otherwise static gene variant).
The absence of large linkage signals and the absence of reproducible genetic associations with nearly all complex diseases may indicate only individual risk gene combinations. It seems to be that we need to listen to another scholar of Popper – Thomas Kuhn — to change the current paradigma.
14-6-07 Finally, Nature published some guidelines for interpretation of association studies
I hope that will never happen to you but when reorganisating my email (from filtered subsets to virtual folder) a large inbox file with ~9000 emails and 1,2 Gb became corrupted.
Spending more than 3 hours on that file, I finally came across Emailchemy that could split the inbox file in chunks of 1000 emails that could re-imported. During this incident, I also found also eml2mbx that allowed to import my cms/vms elm (1991-1992) and windows vines (1993-1997) emails.
Another benefit: My anti virus program repeatedly complained about a virus sitting in an old email folder. Splitting up now this folder in a separate directory allowed to identify the email that had a script attached.
which is even true for negative knowledge, e.g. the knowledge there is no association between factor x and factor y under condition z. As we all know this is being difficult to publish – Technology Review offers some relief:
„Journal of Negative Results – Ecology and Evolutionary Biology“ (JNR-EEB)
„Journal of Negative Observations in Genetic Oncology“
„Journal of Interesting Negative Results in Natural Language Processing and Machine Learning“
„Journal of Articles in Support of the Null Hypothesis“
„Journal of Negative Results in Biomedicine“
„Forum for Negative Results“ (FNR) inside of „Journal of Universal Computer Science“
Do you know how a mechanical clock works? Here is my attempt to explain this to my children:
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The power (the white solid wheel at 4 o’clock) is attached to a series of wheels (black, green, pink) that finally carry the hands.
The clock would run as fast as possible if the power wheel would not limited by a second set of wheels (blue, yellow, red) leading to white escapement, that is leading to a periodic repetitive action allowing the power to escape in small bursts rather than drain away all at once.
The trick is with the special form of the white escapement wheel at 12 o’clock which lifts up the pallet arbor periodically. The pallet arbor has 2 pallets, which enter the spaces between the wheel teeth; it rocks back and forth in a consistent way is it also connected to a pendulum. As each tooth moves in and out of the teeth, it allows the wheel to turn in repetitive actions.
More clocks photos at human clock; we will need this principle at a later stage.