Posts by Steve Lolait

G"Day Taha: I'm fairly sure that 'low copy' in LCRs (repeats classically greater than 1kb at two (duplicated) or more genomic locations) refers to the number of copies found. If you search google images you will find examples of LCRs on various human chromosomes, e.g., http://www.pnas.org/content/105/44/1711 … nsion.html

For those interested in 'junk' DNA, there is a recent interesting comment on the ENCODE data at: http://www.pnas.org/content/early/2013/ … l.pdf+html
("Is junk DNA bunk? A critique of ENCODE" by W. Ford Doolittle).

To be clear about my post above, there is quite a bit of evidence mainly in animal models or cells in vitro - not smoking marijuana -  that active ingredients such as THC and cannabidiol have anti-proliferative and/or pro-apoptotic effects on certain types of cancers.

G'Day Matt:
The use of Igf-1 receptor agonists and other growth promoters as PEDs is contentious and most of us would say highly inadvisable, and as many would know is very much ‘under the microscope’ with the recent press about sport ‘doping’ in Australia and elsewhere. Of course there may be clinical conditions where growth promoters are indicated. Interrupting normal physiological processes to manipulate human aging is something that the scientific community would not normally recommend, even if it is only (!!) because of potential long-term side-effects (e.g., altering normal development, and in the case of Igf-1 blockers, stunted growth) of many compounds or their use is in ‘ethical limbo'. Igf-1 receptor antagonists/pathway inhibitors have been developed and are in the pipeline but I think that these have been primarily worked-up for their potential to inhibit the growth of certain cancers.

Agree with Reetika and David, but I will say that 'back in the good old days' we used to synthesise our own oligonucleotides and the machine was exceptionally easy to use (just screw/clip on a few bottles of reagents, type in your sequence and press a button!), but quality control was sometimes a problem. So an understanding of the machine, reagents and method was essential for trouble-shooting (like for so many other methods in scientific research!). The refined modern machines with, e.g., PC output of synthesis efficiency, etc. coupled to HPLC purification give a lot better quality control.

Some ingredients of marijuana also appear to inhibit the growth of a number of different types of tumors either directly or via inhibiting angiogenesis - here’s a recent paper - http://www.ncbi.nlm.nih.gov/pubmed/23349970 and a recent review - http://www.ncbi.nlm.nih.gov/pubmed/22555283. Long way off a 'cure' though!

There are a number of databases that give the 'official' gene nomenclature, the National Center for Biotechnology Information (NCBI) based in the USA being one of the most widely-used. e.g., if you go to - http://www.ncbi.nlm.nih.gov/gene you can obtain the official gene name (and alternatives) for virtually all known protein-coding genes. For Reetika's example you would just type in platelet activating factor receptor into the search box to obtain PAFR for the human gene name and usually Pafr for the equivalent gene in other species.

As far as the convention of gene naming goes, groups with common research interests often get together and make nomenclature recommendations for the wider scientific community so as to avoid the confusion of multiple names for one gene (common in the past). One such grouping is the IUPHAR database (http://www.iuphar-db.org/), the International Union of Basic and Clinical Pharmacology listings for G protein-coupled and other receptors, and ion channels.
Other groups include the HUGO Gene Nomenclature Committee (http://www.genenames.org/) which gives gene symbols and names for over 33,000 human loci including most protein-coding genes.

Ah Max!! To follow on from David at high [DNA] you also could have an increased amount of 'impurities' (salts, etc) that can affect transformation efficiencies. Do you really think that you can accurately compare the stated Invitrogen effciency using a plasmid (pUC19) prepared by whatever method (how much is supercoiled DNA?) with your plasmid sample? Also, look at the Invitrogen spec sheet - did you follow it exactly?

I posted this question on the Wormbase website (http://forums.wormbase.org/) and the definitive answer has not been forthcoming to date. One suggestion is that perhaps the OP are the initials of a lab worker or colleague/collaborator of some of the earliest people working on c.elegans and the 50 refers to the 50th derivative tested for uracil auxotrophy…or maybe it does not represent a person at all.

Perhaps the O is an ‘O’ antigen that Owen refers to, exposed on the very outer surface of the bacterial cell, one (number 50) of about 160 different O antigens. OP? P as in O Polysaccharide? Grabbing at straws.....

That's not to say that there are no antibiotics produced by bacteria, right? Howard Florey wrote about this in 1947 ("Antibiotics produced by bacteria"; Acta Medica Scandinavica 128: 495-504). Aren't most of the clinically useful antibiotics of natural origin (e.g., aminoglycosides) produced by streptomyces (although I guess a number of these compounds are now chemically synthesized)?

Good question Tracey! I think it would be possible because I imagine that there would be some epithelial cells present from the sperm whale's G-I tract. It may well depend on how long the ambergris has been floating/lying around, though, so that there would be DNA intact enough (survive in a 'hostile' environment) to do a PCR-based test using species/gene-specific primers.

I don’t think the UK has any dedicated ambergris on-line sites such as you can find in New Zealand but there are these people in France who say they will evaluate a picture and/or a small sample - see http://www.ambre-gris.com/index.html (I have no idea how reputable this is).

If your colleague goes to http://science.howstuffworks.com/zoolog … ergris.htm  there is some basic info about ambergris testing, e.g., "there are a couple of tests that you can perform at home to find out if you should even bring that waxy substance to an expert in the first place.

Needle test - heat a needle over a flame for 15 seconds, and then insert it about an eighth of an inch (.3 cm) into the substance. Does it melt around the needle into a pool of thick, black, bubbling liquid? When you touch that liquid, do you end up with a stringy, tar-like residue on your finger? When you reheat the needle, covered in the melted substance, does it let off a white smoke?

Methyl-alcohol test - does a sample of the substance dissolve in hot methyl alcohol and crystallize when the alcohol cools?

If the substance passes those tests, the next ones take place in a lab. Chemists will test for benzoic acid and cholesterol in the sample. If the amounts are indicative of ambergris, it will usually be tentatively confirmed as ambergris at this time, although perfume companies will typically order more chemical tests before purchasing the would-be whale vomit. Some experts, though, say that the only test that can absolutely identify ambergris is extensive experience with the look, feel and scent of it.”

As to a public lab that could might be able to do testing perhaps contact Defra at: http://vla.defra.gov.uk/ and ask if they could point your colleague in the right direction?

As far as I am aware, the iDCs are derived from bone marrow haematopoietic stem cells, like lymphoid and myeloid DCs, and the fDCs are of mesenchymal origin.

Here’s two recent reviews that touch on the origins of DCs that may be of interest -
http://jem.rupress.org/content/209/6/1053.long
http://www.ncbi.nlm.nih.gov/pubmed/20193011

As Reetika says, there is a lot of functional, genetic and phenotypic diversity in DCs. For example, one recent study (there are many earlier studies looking at DC plasticity) using one stimulant and looking at the expression of different gene markers in cell populations highlights that common myeloid precursors can give rise to ‘conventional’ or classical DCs (cDCs) and plasmacytoid DCs (pDCs) whereas common lymphoid precursors produced only a few cDCs but also pDCs; see - http://www.ncbi.nlm.nih.gov/pubmed/23053574

In theory angiogenesis inhibitors (e.g., directed to some growth factor receptors)  sound like a great idea, and a number of drugs have FDA approval in the USA or are undergoing clinical trials, but in practice there have been a number of problems. One is local (or systemic) side-effects to normal tissue, and in the last couple of decades people have been working on specifically targeting tumor cells (e.g., inhibiting/neutralising angiogenic factors) with monoclonal antibodies and/or targeted drug-delivery systems (e.g., liposomes/nanoparticles) - I don’t know how successful either has been but I doubt they have resulted in complete remission - perhaps David could comment?

There is quite a lot of literature on the expression of class I (including non-classical) and II MHC antigens by neurons, glia and other cells (e.g., endothelial) in the brain. Some of the ‘non-immune’-type functions that David mentions include roles in synaptic plasticity and behaviour such as social recognition. e.g., -

http://www.nature.com/nrn/journal/v5/n7 … n1428.html

http://www.ncbi.nlm.nih.gov/pubmed/16337283

I would add that early life stress (ELS) such as child abuse and maternal separation/deprivation can have profound effects on behaviour (particularly those that may be stress-induced or compounded by stress, such as anxiety-like behaviour and depression) later in life and can be associated with other conditions such as cognitive impairment and psychiatric illnesses (to name just a few) in adult life.

ELS can produce persisting changes in the methylation of certain genes (‘epigenetic programming’) that can alter their activity, especially some that are ‘stress-related’ such as brain-derived neurotrophic factor (BDNF) and vasopressin. Studies in rodents have shown that those that have experienced ‘abuse’ can grow up and mistreat their own offspring, and that their offspring also have significant DNA methylation (e.g., see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056389/ for one example) - the epigenetic status of particular genes in the previous generation may influence the next generation!

There is unlikely to be only one "authoritative publication on the matter of shared DNA".

A good reference source on genomes in general would be something like the National Center for Biotechnology Information (NCBI) @ http://www.ncbi.nlm.nih.gov/genome?term … roglodytes

where you will find a number of publications on the chimpanzee genome project. For example, “Sequencing the chimpanzee genome: Insights into human evolution and disease” by Olson & Varki (Nature Reviews Genetics 4: 20-28, 2003)(available on-line) ia an easy-to-read review.

Ah, the 'good old days'. Before the advent of PCR we made genomic and cDNA libraries which contained thousands-millions of copies of DNA (in the case of cDNA libraries, copies of the protein-coding mRNA) to clone the gene(s)/cDNAs of interest. When everything went well, including the construction of the libraries, this could take a few months or longer! The libraries were usually packaged in bacteria so these could be propogated to give millions of copies of the DNA of interest to obtain sufficient amounts for further manipulations (such as inserting foreign DNA into cells).

To detect genomic/cDNA we could do southern blotting (days-weeks) and mRNA could be detected by techniques such as northen blotting, dot blotting (northern blotting without size discrimination of the mRNA) and in situ hybridisation histochemistry (ISHH) (visualising mRNA in cells or tissue sections) - again these experiments take days-weeks. Note that these techniques are still in use today, and in fact some like ISHH are extremely useful to give the spatial resolution of mRNA (e.g., what cell type in a particular tissue is expressing a gene). However, using a method such as ISHH it can take months to visualise mRNAs that are not abundant (say less than 10 copies/cell).

It is not always necessary to have millions of copies of DNA at your disposal, but PCR allowed us to do a lot of things more quickly (within hours), from detecting minute amounts of DNA (popular in forensic medicine) and obtaining quantities of DNA for further studies, to DNA mutagenesis and detecting gene homologues within and between species.

The cell behaves as a “Ca2+ buffer” using energy to keep the cytoplasmic Ca2+ level low so that it can be rapidly increased to regulate Ca2+-dependent processes in the cell. In general, the free extracellular Ca2+ concentration is >1.5mM or so whereas the free cytoplasmic Ca2+ levels tend to be < 100nM (the concentration of Ca2+ will be higher in intracellular organelles such as the endoplasmic reticulum in which it is stored). This difference is based on a phospholipid bilayer impermeable to Ca2+, Ca2+ sequestration and efflux mechanisms, and Ca2+binding proteins.
Rises in the intracellular Ca2+ depend on the release of Ca2+ from intracellular stores, such as from the endoplasmic reticulum or muscle sarcoplasmic reticulum, or golgi apparatus* and/or Ca2+ influx across the plasma membrane (e.g., via receptor-activated or voltage-operated Ca2+ channels). The relative importance of these two pathways is cell type- and stimulus-dependent. The release of Ca2+ from intracellular stores is often triggered by the activation of the enzyme phospholipase C - as happens when many neurotranmitters and hormones bind to their corresponding receptors (often G protein-coupled receptors) - and involves the activation of various types of Ca2+ channels and other proteins, and mechanisms to terminate the Ca2+ signal (e.g., Ca2+ extrusion via Ca2+ ATPase). 

I hope that helps!

http://www.sabiosciences.com/pathway.ph … _Signaling

shows a picture that will give you a feel for the complexity of intracellular Ca2+ signalling.

* other organelles that have Ca2+-handling machinery include the nucleus, mitochondria and lysosomes.

It’s been quite a while since I have been in Melbourne so I can only go into a few generalities. There are certainly opportunities to work with large animals (sheep, cows, horses, etc) at some institutions including universities and places like the CSIRO, but these may be more geared to post-graduate work. I doubt there is much, if anything, on big cats - although there have been quite a few ‘big cat sightings’ in Victoria and other States over the years!! Melbourne has a number of universities as you are aware, and most students studying biology I guess would attend Melbourne, Monash or Latrobe. If you are interested in a basic zoology-type degree then all are probably O’K (although my bias would be Monash since it my alumni!). However, something like this following course may interest you more - http://www.latrobe.edu.au/courses/wildl … on-biology
As Reetika says, I would initially go on-line and look at Faculty of Science admission requirements - if that does not help (and it may not since I gather you already have a first degree) contact the relevant admission offices directly by email or phone.

P.S. cystine is the dimeric amino acid formed by the oxidation of two cysteine residues that covalently link to make a disulfide bond.

I like John's ideas! To fit in with the brain pathology, how about a condition similar to a 'slow' virus-based disease, transmitted by a new generation of prions that are present in the soil (hence food and water). The prions would inactivate/regulate some essential proteins in the body, which remain relatively hidden/'dormant' in normal neural tissue until activated by our responses to stress (and thus become exposed to the infectious agent).

G'Day Dan:
A colleague who is an expert on LTP and LTD recommends an old paper that he says is easy to follow and covers a wide range of points related to the topic providing basic definitions. Google “Neurobiological principles of learning and memory” by Brunelli and coworkers to retrieve manuscript.

An article "Weight, volume and center of mass of segments of the human body" by Clauser, McConville & Young (1969) from the United States Air Force is retrievable via Google. 13 male cadavers studied - Table 11 (p.52) gives entry 80 (weight of leg) while entry 158 gives weight of leg as % of total body weight = 14.3-17.5% in their study. I imagine that places like NASA would have even more statistics.