G'Day Jacob: While I don’t know what is growing in your beverage my guess would be that it is a mold (which can grow as white, fluffy masses) or yeast rather than bacteria. These soft drinks have a high concentration of sugar that many bacteria don’t like (although some strains of staph love it!), and at least for a while the beverage is/was probably acidic. Some yeast, molds or bacteria (e.g., acidophiles) would likely enjoy this environment but most would not. 

I imagine once the beverage dries however all sorts of bugs could thrive in it.

see also - http://www.bcnlabs.com/beverages

There is loads of info about agarose gel electrpohoresis found by a simple search on-line, including the Wikipedia entry. I will say that the resolution of DNA bands are affected by a number of factors other than agarose concentration (and there are different types of agarose!), such as the amount of DNA loaded and the comb width.

As you’ll know from your reading Kathy there are many different strains of P.multocida, for which there are serological and more recently genetic (e.g., PCR and whole genome expression profiling including DNA sequencing) tests. The severity of effects can depend on the strain, so a virulent strain in one species could have less harmful effects in another, or 2 different strains may not have identical effects in the same species. From a brief read of one of the articles you probably came across (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122976/) 2 typed (e.g., PCR, DNA sequence analysis) avian F strains were able to infect rabbits in a laboratory environment. In a field setting I think that you would have do typing to be sure of the bacterial strain involved (although environment/proximity factors may be highly suggestive).

As a general point Yujin, when we watch a person perform a lab technique with which we are unfamiliar we should ask questions at the time (or subsequently) to make sure we understand what is going on (e.g., “what is in that solution?”). Your question can probably be answered by a quick search on-line, even the Wikipedia entry on 'DNA extraction' will help you. Briefly, genomic DNA is soluble in most DNA genotyping-extraction buffers and you need to precipitate it out of solution, which subsequently requires centrifugation to isolate the DNA (and perhaps other material that can be reduced/removed if required).

The classical Hershey-Chase experiment is something a little different, involving incorporation of radiolabelled ‘DNA’ by bacteriophage into bacteria (which were pelleted by centrifugation - note that bacteria will settle to the bottom of a test tube slowly even without centrifugation)

see - Hershey AD and Chase M (1952). Independent functions of viral protein and nucleic acid in growth of bacteriophage. J Gen Physiol 36: 39-56 (this can be downloaded - not many scientific articles from this era can be!).

There are some early strategies using CRISPR to target drug-resistant bacteria (e.g., by ‘attacking’ antibiotic resistant gene repertoire). One problem are current delivery systems and whether they will be ‘fast’ enough to overcome a quickly evolving bug population. see -

http://www.the-scientist.com/?articles. … nd-Phages/

http://www.nature.com/scibx/journal/v7/ … .1198.html

(posted in General Biology)

Also there will be differences between and within populations - there are hundreds of human olfactory receptors (exhibiting a range of polymorphisms) and hundreds of volatile chemicals found in food. Ajna, in your type of experiment do you obtain the same result(s) when you take into account shape and texture - e.g., if the products are emulsified?

(posted in General Biology)

And many people with smell disorders have problems with their sense of taste - e.g., see - https://www.nidcd.nih.gov/health/smell-disorders

EBV is able to induce a T-cell independent immunoglobulin response by B cells, i.e., antibodies can be made to some EBV-encoded proteins without T-cell involvement. Another example of a T-cell independent antigen would be bacterial lipopolysaccharide (LPS), and if you search on google for 'T-cell independent antibody responses to viruses' you will come up with other examples.

That does not mean that EBV can't infect T-cells, or that there no T-cell responses to EBV infection.

Considering salt alone, as Reetika says bacteria and other microrganisms in general survive a range of salt concentrations. Microorganisms called halophiles optimally grow in the equivalent of 0.85M NaCl (~5% w/v) and tolerate up to the equivalent of 5M NaCl (~26% w/v), concentrations well above that of isotonic NaCl (~0.9% w/v). It will depend on the type of microorganism but I doubt you will normally encounter many microorganisms that will be happy in saturated NaCl! (~26% w/v, ~5M). I think most strains of E.coli don’t like NaCl concentrations much above 0.5% but these may not necessarily kill them - there are many variables such as growth matrix (e.g., liquid/solid), stage of growth, temperature and possible ‘adaptation’ to high salt concentrations.

I can only offer generalities here! You can certainly make antibodies (which are proteins) that can bind (and may block function) to all three of these surface receptors (see - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539746/), but you would have to do some reading to establish whether one antibody or vaccine could be/has been produced against all three - e.g., is there enough similarity between the antigenic epitopes of the three receptors?

There may also be antibacterials, not necessarily proteins, already in existence that recognise IsdA/B/H to interfere with heme binding and/or transport-function, although you would not classify many of these drugs (such as porphyrins - see http://www.ncbi.nlm.nih.gov/pubmed/11178343) as true receptor ‘antagonists’ (e.g., they may bind to Isd’s to ‘piggy-back’ into the cell, mimicking the binding properties of the natural ligand, and there exert antimicrobial activity).

As to receptor ‘antagonists’ in general there are protein antagonists that can block the activity of any number of receptors particularly in a closely-related receptor family, if there is sufficient structural similarity in the antagonist binding domains. A pan-specific receptor antagonist may often have differing affinities between receptors.

Designing such an antagonist has traditionally been based on identifying a candidate from a screen of ‘lead’ compounds that might bind to a number of receptors. It is then usually chemically refined to increase its affinity and specificity to one receptor (often to reduce off-target effects). As the 3D structures of more and more receptors are being elucidated a lot of effort is being invested in computer-aided molecular modelling (‘locking and docking’) of receptor ligands. This is mostly the remit of highly specialised labs.

see also - https://en.wikipedia.org/wiki/Antimicrobial_peptides

Also some Universities have animal units that may allow volunteering work with small and/or large animals.

In addition, this article - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732559/ - gives references that highlight substratum effects on microbe growth in a biofilm (e.g., sometimes better attachment on nonpolar surfaces), and discusses some variables including type and hydrodynamics of the bug-growing medium and type of microbe (encompassing cell surface charge).

(posted in Plants & Fungi)

G'Day Karin: I think that the garden strawberry and basil (there are many varieties) would be too genetically distinct to form viable hybrids, coming from different plant families. But from a 'MasterChef' perpsective it would be a great idea!

(posted in Mammals)

Here is also a quite good, brief summary that backs up what Andy is saying - http://www.ncbi.nlm.nih.gov/books/NBK11117/

Note that this talks about postsynaptic effects. GABA is the major inhibitory major neurotransmitter in the brain, which it can do by activating GABAA channels (composed of a variety of subunits) on, I think, mostly post-synaptic membranes, but also at pre-synaptic and ‘extra-synaptic’ sites. There is another type of GABA receptor, the ‘metabotropic’ G protein coupled GABAB, which can also mediate pre- and post-synaptic inhibition.

Excitatory and inhibitory neurons can synapse on the same neuron - this is not uncommon. And there is a lot of input, e.g., from neuropeptides and other substances like a major inhibitory transmitter such as endocannabinoids (e.g., activating the cannabinoid CB1 receptor in the brain, one of the most abundant central G protein-coupled receptors), that modulate either excitatory or inhibitory synapses.

Quite often you have to look at synapses in the brain as part of a network, e.g., inhibitory input onto an excitatory neurone (e.g., GABA onto a glutamate neurone), excitatory input onto an inhibitory neurone, inhibitory input onto an inhibitory neurone, etc.

I agree with David - in the literature where ‘beta forms’ of keratin have been described in humans (e.g., see - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304386/) people are usually referring to ‘beta sheets’ or ‘beta turns’ (the secondary structure form) rather than beta-keratin proteins themselves which have different amino acid compositions to the alpha-keratins. There are lots of distinct, structurally-related forms (over 50 functional in humans; nomenclature KRT) of keratins whose amino acids are arranged in an alpha-helical conformation, but DNA/genome databases (e.g., NCBI; http://www.ncbi.nlm.nih.gov/) show no entry for a human ‘beta keratin gene’.

By the way, as you probably know keratins are a major component of intermediate filaments, one of the 3 major types of cytoskeleton fibres in cells (the other two are the actin microfilaments and the microtubules) - there are some stunning pictures of these on-line (google image search keratin intermediate filaments).

Dopamine receptors are members of the G protein-coupled receptor (GPCR) superfamily. GPCRs have a dynamic structure that can assume a spectrum of conformational states. Upon ligand binding there are changes in the GPCR that lead to structural re-arrangements that facilitate interaction with intracellular effectors (as David points out) such as G proteins, kinases and arrestins that leads to the activation of a plethora of signalling molecules and cascades. These structural changes have been determined by biochemical, biophysical and mutagenesis studies and validated more recently by X-ray crystallography of a number of GPCRs.

Dopamine receptors comprise 5 structurally-related members and fall into 2 classes; the D1-like (D1 and D5) and D2-like (D2, D3 and D4). The genes for the former are intronless while the D2-like receptor genes have introns (interrupting their protein-coding sequences) so they can have alternatively-spliced forms that can confer different pharmacological properties. Subleties in the orientation of the 7 transmembrane helices of each dopamine receptor as well as differences in intracellular and extracellular domains confer the pharmacological and biochemical properties that make each dopamine receptor unique. Broadly speaking D1-like receptors tend to bind Gs protein to activate adenyl cyclase (raising cyclic AMP) whereas D2-like receptors bind to Gi/o proteins to inhibit adenyl cyclase, but the D2's can also bind to other G proteins such as Gq (which often leads to intracellular calcium mobilization).

Where dopamine receptors 'live' is obviously integral to their function. They may reside on different tissues or brain regions, on separate cells, or be located pre- or post-synaptically. Some dopamine receptors may be co-expressed in the same neuron and may interact at the physical level (e.g., by receptor dimerization) or cross-talk via converging intracellular pathways. e.g., D1 and D2 receptors have opposing effects on intracellular sodium in striatal neurons in the basal ganglia (http://www.ncbi.nlm.nih.gov/pubmed/10700253). So the final functional output of a cell may be the result of the coordinate activation of dopamine receptors (expressed on the same or different cells) and in collaboration with many other receptors and intracellular signalling pathways (bare in mind that the average neuron expresses hundreds of receptors!).

There are many good references on dopamine receptors (e.g., see - http://pharmrev.aspetjournals.org/conte … 182.full). There is also a good general database on all GPCRs (http://www.guidetopharmacology.org/) that summarizes details on the 5 dopamine receptors.

From a quick look at Reetika's link I don't think it says how the DNA sequence for insulin was determined. In the very 'early' days of recombinant DNA technology fairly standard procedures were used. I think you will find that in the late 1970's scientists would have found the 'right' DNA sequence corresponding to the mRNA sequence for insulin! e.g., they cloned the cDNA for the insulin precursor mRNA.

I haven't searched for the papers (there will be extensive references to these on Google) to check the methods used but the basic idea would have been this: you knew the protein sequence for insulin (determined by Sanger in the 1950's), so make a DNA probe or probes corresponding to that protein sequence and use these probes to screen either a cDNA (constructed from mRNA) or genomic DNA library expressed in bacteria; then isolate bacterial clones that bind the probe(s) and sequence their cDNA or genomic DNA inserts. In that way you would find clones that have the DNA sequence corresponding to the probes you used in the first place, and expand them so that you would have millions of bacteria that would express the insulin cDNA or gene (that would be transcribed into insulin mRNA and translated into insulin protein). I think the DNA (hence mRNA) sequence for insulin was first obtained for rat, followed soon thereafter by human. Hope that helps!

FYI Ece, although not the same as molecularly engineering a construct to insert bacterial DNA into our genomes, there is evidence for 'natural' lateral gene transfer of viral DNA into the human genome - see
http://journals.plos.org/ploscompbiol/a … bi.1003107 and
http://journals.plos.org/plosgenetics/a … en.1003877

You haven’t provided us with some details, e.g., sample (sections (thickness?), cells), concentration and age of DAPI, incubation time, fluorescence filters, etc. Irrespective, DAPI staining is usually best at around neutral pH so one thing you could do is equilibrate your sample in a phosphate-buffered saline, pH7.0 (note that not all PBS buffers are the same!) for 5-10min or so, perhaps with 1-2 changes of PBS, prior to DAPI staining (and destain in the same PBS-like buffer; some samples require very little, if any destaining). I have no experience in destaining any DAPI-stained sample in the buffer and temp you specify, and suspect that this may be more related to staining/destaining nucleic acids in gels (e.g., http://nar.oxfordjournals.org/content/6 … abstract). In any event note that most (but not all) people would use different dyes to stain nucelic acids in gels, many with less potential toxicity compared with DAPI (e.g., see the ThermoFisher Scientific ‘The Molecular Probes Handbook’ Section 8.4). Hope this helps!

(posted in General Biology)

You may also want to look at this very recent commentary on the non-medical uses of brain stimulation in Nature - http://www.nature.com/news/brain-power-1.19475

(posted in Mammals)

G'Day Shelby: A previous post on this forum may help - http://www.askabiologist.org.uk/answers … hp?id=4190

Interesting question Kaushik, and very ‘specific’ that can probably be answered by your lecturer/tutor (assuming that you are a University student) or by an on-line search! As you likely know the MAPK pathway has been reasonably well-conserved across evolution. According to a recent computer simulation study (see - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC41288) the 3-tiered module is both robust and adaptable (for “random mutations to generate phenotypic variation during evolution”). In terms of the tight control subserved by dual phosphorylation, the same article suggests that a distributive phosphorylation system is good at amplifying input signals (e.g., see also an article on activation mechanism of ERK2 by dual phosphorylation - http://www.cell.com/abstract/S0092-8674 … 980351-7).

I agree with Nick, the staining of this prep does not allow for clear identification of some cells. Many of the apparent RBCs appear to have a 'bioconcave' morphology as expected. The circled cells, if RBCs, could be immature, as what Nick describes as ribosomes are usually lost in mature RBCs - so these cells could be WBCs but it is not clear (if I look long enough, especially at the bottom one, they almost look like some of the cells without 'stippling!!; if I look again it seems that they are different)!

To add, another popular use of sequence-specific oligos is PCR (either end-point or 'quantitative' as in qPCR). We often use various oligonucleotide-design programs and DNA databases to check oligo specificity for a single gene product; i.e., using these programs you can usually determine whether your oligo has the potential to 'cross-react' with genes other than the one you are interested in. This is aided by the fact that the sequencing of some genomes (e.g., human) has essentially been completed. We use the word 'stringency' to describe the conditions under which the oligo will bind to a specific DNA (or RNA) strand - a sequence-specific oligo can often be used at 'high stringency' (typically low salt concentration and/or high temperature used in your experiment) so that cross-reaction can be minimised, although on occasion you may want to detect a sequence that is common to a family of genes.

In my field of research there is quite a 'famous' example of how a gene may change behaviour. The distribution of vasopressin and oxytocin receptors in the brain can exhibit profound species differences; e.g., the montane and prairie vole have strikingly different patterns in vasopressin V1a receptor expression. It has been shown that vasopressin is important for affiliative behaviour, such that this ‘neuro’hormone increases olfactory investigation and grooming (towards a female) in the highly social, ‘monogamous’ male prairie vole but not in the relatively asocial, ‘promiscous’ male montane vole. If you engineer a mouse (relatively ‘promiscuous’) to express a prairie vole-like V1a receptor distribution in the brain (e..g., by introducing the prairie vole V1a receptor gene into the mouse) then this animal has pro-social response to vasopressin, i.e., behaves more like a ‘monogamous’ animal!

This does not mean that only the V1a receptor is responsible for pro-social behaviour (or for example, that generating a prairie vole-like brain distribution in a mouse has not altered other genes and/or neural wiring) but it does seem to suggest that changes in the (pattern of) expression of a single gene can influence some types of behaviour.

See - http://www.ncbi.nlm.nih.gov/pubmed/10466725

(posted in Genes, Genetics and DNA)

Yes, for humans the amount of purine bases equals the amount of pyrimidine bases, so A + G (or C + T) is about 50%. As far as I am aware there is some overall nucleotide bias in a variety of genomes, where e.g., there are high (greater than 50%) and low G/C content bacteria, and the human genome is less than 50% G/C. It is not necessarily a 1:1:1:1 ratio of A:C:G:T (or 1:1 for A:G; or 1:1 for C:T).

[for a basic reference see Table 2.2, p43 “Genetics: Analysis of Genes and Genomes 7th Ed, Hartl & Jones, 2009]

I’m not sure about your terminology/details here! For starters 'probes' usually equal primers in a regular PCR reaction (unless you had internal 'probes' to the PCR'd amplicon). And if you are doing a multiplex reaction are the two temps referring to one probe set? Or do you mean the amplified PCR products?

When we are talking about optimal annealing temperatures in PCR we are usually referring to the annealing temp of the primers. This temp may not be the same as the Tm of the amplified product (differential ‘melt curves’ in multiplex reactions are useful in qPCR!). For one set of primers you would hope that the melting temperatures were reasonably closely matched - there are many primer design programs out there that can help you achieve this. Yield can be increased by a number of ways such as increasing cycles and altering salt (e.g., MgCl2) concentrations, both of which may lead to an increase in non-specific products. Extension times depend on the length(s) you are amplifying and the type of taq polymerase. Changing primer length would not usually affect product yield, but could alter G/C content enough to get a better primer pair Tm match, and optimizing (not necessarily increasing) dNTP, primer and template ratios certainly can affect results.

Please get back to us if you have further questions!

(posted in General Biology)

There are some excellent questions here! The first thing to say is that in general fusing cells is a relatively inefficient process and that the detailed mechanism(s) underlying it are unknown. From some of the earlier experiments polyethylene glycol (PEG)-induced cell fusion involves dehydration of membrane surfaces forcing close contact between membranes, and it appears that the plasma membrane AND then cytoplasmic compartments become one (http://jcb.rupress.org/content/96/1/151.long; http://www.tandfonline.com/doi/pdf/10.1080/096876899294508), and I would imagine that this includes the ER.

The ES-somatic cell hybrids that result from fusion (using PEG, for example) appear to adopt the transcriptional profile of ESCs with apparent silencing of many (but not all) somatic genes (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030652/). I think that in some cell fusion hybrids there may be some evidence for the organelles of one cell adopting the ‘shape’ and polarity of the other, which may involve alterations in the cytoskeleton - I don’t know if this happens in ES-somatic cells. PEG itself induces cytoskeletal reorganisation in many cells (e.g., see - http://ncbi.nlm.nih.gov/pmc/articles/PMC3736723/). I also don’t know how the various organelles ‘find’ each other - perhaps there is a high level of ‘intermixing’ which leads to unviable hybrids, and the ‘specificity’ is based on physical/chemical interactions that underpins viability/growth. This article - http://www.sciencedirect.com/science/ar … 5492900028 - shows the ultrastructural changes during PEG fusion of two cells (including a nice figure (3) showing intermediate nuclear fusion and possible mitochondria-nucleus fusion).<cite></cite>

Tom, alcohols such as ethanol and methanol can alter cell mebrane permeability to various substances by interacting with lipids. The effect is concentration-dependent.

I would favour (1) and (2) - as far as I am aware there are also 'no native' koalas in the NT or WA.

P.S. The wikipedia entry on Koalas states that there is fossil evidence for koalas in WA, but that 'they were likely driven to extinction in these areas by environmental changes and hunting by indigenous Australians'.

Autoimmune (AI) reactions are usually caused by your body's immune system recognising 'self' as foreign, so potentially anything (including a virus that might appear 'benign') that can be recognised as 'self' (e.g., the virus has antigenic epitopes that are similar to one or more of your own proteins) or alter your body's proteins so that they are recognised as foreign, can cause an AI reaction. A good number of AI conditions are tissue-specific although I can't think of one restricted to a hand or leg (!) off-hand, but bare in mind that the causes for many AI conditions are not known.

There are a few interesting relevant comments about species differences in NMJs (see 'Intracellular communication in the Nervous System' (2010), Robert C. Malenka; p186 observed on-line googling ‘neuromuscular junction folds in birds’) re. folds increasing surface area and a possible reciprocal relationship between the quanta of Ach released at the NMJ and the intensity of postsynaptic folding (the more Ach released the fewer folds expressing nicotinic Ach receptors required to ‘amplify’ its effects, as in some fish and birds, and I imagine that this would be muscle-dependent).

Also, free testosterone has a half-life of only minutes in plasma. Most of the hormone is bound to proteins which can serve as a circulating ‘sink’ and affect its bioavailability. Various testosterone derivatives have half-lives of days.

It's a bit difficult to decipher these figures and know what the author is referring to - my guess (but I may be completely wrong) would be some type(s) of 'coated pits' or endocytotic vesicles, membrane blebs/invaginations that are involved in such things as phagocytosis, pinocytosis (cell 'drinking') and/or receptor-mediated endocytosis/receptor recycling. If they represented these structures then we do know something about what they do! I would contact the author and see if he can provide further details!

(posted in General Biology)

I have never seen 'adrenosine' in any context - must be a typo! There is 'adrenaline' and 'adrenoceptors' though...

If you search 'plasmid DNA' in the upper right-hand side search box you will find a number of posts that address this question.

Fair enough!

David, I've often wondered about this sort of statement - 'it matters little what undergrad degree you do in the broad area of biology..' in the context of applying for post-graduate degrees. Don't you think that it might be advantageous to some degree if, e.g., you wanted to apply for a post-grad qualification in something like psychology, that you had studied psychology at some level as an undergraduate? (at the very least it would give the impression of some on-going interest in the field?).

Just to add, there is also evidence that steroid hormones such as cortisol, aldosterone and oestrogen may act at, or near, the cell surface (or other intracellular sites) involving 'fast' activation of second messengers such as calcium, cAMP and other pathways. The type(s) of receptors involved in these 'non-transcriptional' effects is hotly debated, e.g., they could be 'nuclear' receptors or variants thereof acting outside the nucleus, or novel receptors. An example of the latter appears to be the G protein-coupled oestrogen receptor, GPER.

I’m not sure that I quite understand your question! If we take dopamine as an example, this catecholamine binds to 5 subtypes of receptors, D1-5. These 5 receptors are structurally very similar but have different pharmacological profiles, i.e., they are all activated by the endogenous ligand dopamine but they bind different exogenous antagonists and agonists with different affinities. Subtype-specific antagonists may bind to different places in the D receptor(s). The D receptors also have different tissue distributions, although these may overlap in various places, e.g., in a brain region involved in reward called the striatum. As far as I am aware no D receptor is restricted to one tissue (there are few genes that are truly tissue-specific), so in theory a general antagonist to D1-5 would block dopamine function in multiple tissues, as would a specific antagonist against one D receptor subtype. This can give rise to side-effects in one or more tissues that may be detrimental in terms of therapeutic treatment, or may be well-tolerated. Side-effects may also arise, e.g., if the D receptors are functionally complexed to different proteins that have different (non-dopamine) functions, or if the D receptors are an intermediate in a (non-dopamine) physiological pathway. Please post again if you need further clarification.

I agree with you, I think this area of biology is fascinating, but it is early days. I would imagine that there are not a lot of scientists in the UK directly working on this - however a cursory search found a self-funded PhD project at the University of Surrey (http://www.findaphd.com/search/projectd … PJID=58482), and a workshop a few years ago (http://www.ias.surrey.ac.uk/workshops/quantumbiology/), so there is obviously interest.

There is increasing emphasis on multi-disciplinary approaches in biological/medical research, such as mathematical modelling of biological processes. This article on quantum biology - http://www.nature.com/nphys/journal/v9/ … s2474.html - highlights photosynthesis and magneto-reception for bird navigation. As to subject areas in Biochemistry I have no idea which specific ones would be the most appropriate for a post-graduate career - I think a general grounding in genetic and cellular processes would be important. You could contact the people at Surrey, or others listed in the workshop noted above, and ask for their advice (?).

Just to add, you should be able to find PhD opportunities and/or projects quite easily at most UK universities, e.g. at Bristol you could start at - http://www.bristol.ac.uk/study/postgraduate/. You may have to search individual Faculties/Schools to find what they offer re. postgraduate study and what PhD studentships may be available, or perhaps you might be interested in a particularly field and you can search that as well. Many applicants have not done a year in industry. A first at under-graduate level is obviously desirable to make you more competitive, but if that doesn't happen it is not the end of the world (you might have to take and do well in a Masters degree which can have a research component). Please post again if you have any other questions.

Re post-graduate funding for non-EU students, yes it is extremely competitive but many universities post links to various international funding bodies, often nationality- specific. e.g., for Oxford - http://www.ox.ac.uk/admissions/graduate … holarships

If I am reading this right, I don’t quite agree with you Reetika! If we are talking about the sodium-potassium-ATPase pump for example, it does appear to get phosphorylated via PKA sites - see http://www.sciencedirect.com/science/ar … 9310003054

Also see the Wkipedia entry on this ATPase.

I think that the input of new, naïve T cells into the lymphocyte pool from the thymus declines with age, that these cells are relatively long-lived compared to the effector and memory T cells, and that some memory T cells may actually return to a resting state. However, I see from this article - http://www.pnas.org/content/106/43/18333.full - that a “substantial naïve T cell pool is maintained even in aged animals”. I would imagine that the commitment (and number) of memory T cells will depend a lot on the type and degree of antigen exposure during your lifetime. For a review on human memory T cells see -http://www.nature.com/nri/journal/v14/n1/pdf/nri3567.pdf

Here is a cautionary note about 'touch DNA' being used in forensic medicine - http://www.nature.com/news/forensic-dna … le-1.18654

G'Day George: As lists go there are many more metabotropic (e.g., this would include G protein-coupled receptors (GPCRs)) than ionotropic receptors. However the ionotropic receptors tend to be a lot more abundant in the brain in terms of gene and protein expression. There will be various notions of what people consider an ‘average’ neuron and if you take both receptor classes (and their subtypes) there will be brain region-specific expression patterns. Also, some neurons may express most (if not all) of these receptors, but there will be differences in the absolute numbers, perhaps averaging hundreds to thousands of one type of ionotropic (e.g., GluA2) and metabotropic (e.g., mGlu1) receptor per neuron. There will also be variants (e.g., splice) of many types of these receptors.

In terms of gene expression, sequencing of single neurons (i.e., transcriptomic profiles) has been performed in a few brain regions and this reveals a complexity that we may not have imagined based on pharmacological studies alone. For example in some individual hypothalamic (preoptic area) neurons it appears that the genes for over 250 neurotransmitter receptors (mostly GPCRs) and ligand-gated ion channels are expressed - and there are hundreds of additional hormone receptors. In this particular example - see http://www.ncbi.nlm.nih.gov/pubmed/20970451 - there were over 150 different non-olfactory GPCRs and around 90 different ion channels per neuron. Many of these receptors may oligomerise with each other, or to a different receptor type to alter their pharmacology. One challenge for neuroscientists is to establish how many receptors in a neuron are functional.

One of the best sites for information on receptors that people in the field(s) use is - http://www.guidetopharmacology.org/

G'Day Lauren: Have a look at this very easy to read article - http://www.nature.com/scitable/topicpag … -14397318; and this one (especially the Intro) - http://elifesciences.org/content/3/e02009, which emphasises the possible role of diffusion.

Looking on-line the directional movement is more consistent with a ciliate as well!

Titanium and other metals (or alloys thereof) have been used for bone replacement (e.g., in hip joints), a key issue being the extent of metallic debris fragments generated if it is a metal on metal implant - small fragments are also generated with plastic polymers. Titanium has been used because of its strength (e.g., ability to support weight), resistance to corrosion/degradation and biocompatibility, such as ability to maintain normal cell and regenerative functions. So a certain degree of porosity is required and this will also affect cell seeding/migration, matrix deposition, vascularization and movement of nutrients.

David Wynick may be able to comment, but I think metal on polyethylene implants are still very popular because of cost (lower than titanium)-performance ratios over the lifetime of the materials in situ. I would imagine that plastics can be engineered to have a similar porosity and other properties charactersitic of metal implants. I guess surgeon preference may also come into it (e.g., expertise/familiarity in one procedure over others)?

Titanium has also been used as a mesh for metallic scaffolding in bone regeneration. Porous scaffolds provide a 3D-framework for reparative cells and/or regenerative factors, and they may have to be load-bearing as well. For a scaffold that has been introduced with cells in situ (e.g., stem cells) it may also have the capacity to restrict movement of these cells away from the implant site. Bone scaffolds can be modified to make them more biocompatible, e.g., with the introduction of biological or synthetic polymers and/or cells. Here is a quite comprehensive article that covers the properties of various metal bone scaffolds - https://www.mdpi.com/1996-1944/2/3/790/pdf. Costs are a consideration - from that article I see that tantalum (don’t remember this from the Periodic Table!!) has been used in bone implants, has excellent biocompatibility but has high manufacturing costs (see - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883027/).

For an example of a type of titanium mesh cage for fractured lumbar vertebra used in patients with osteoporosis see - http://www.hindawi.com/journals/bmri/2014/853897/.