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Olfaction - Science topic

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There is an abundance of new scientific literature that has been published (over the past year and a half) on new clinical research developments of electronic-nose (e-nose), or artificial olfaction and related technologies, for the early detection and diagnosis of Covid-19 coronavirus infections in human patients. This question centers around the idea of whether any of these research approaches have actually been further developed (beyond proof of concept) to the extent that new diagnostic methods (based on e-nose instruments) are already being used in clinical practice. I am not looking for literature (published research) on experimental trials, but rather actual examples of clinical uses (locations of medical facilities and technologies used) that have already been implemented in a known clinical setting or for point-of-care testing (POCT).
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Antti, thanks for informing us about these new devices for detection of Covid-19. It would be very useful to know if there were particular VOCs that might serve as potential new biomarkers of this disease, within certain known chemical classes, that may have been identified among those volatile compounds detected by these particular devices. Thorough chemical and metabolomic analyses of the breath volatilome from healthy vs. Covid-19 infected patients could provide useful clues of the human metabolic pathways most affected by Covid-19 pathogenesis.
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Retronasal flavor is sensation referral via mouth. Retronasal is not only volatile substances, but airborne containing particles, liquid drop. Retronasal substances could be recognized after swallowing.
GC-MS-O filters many interesting flavoring substances for retronasal sensation during sample preparation. Orthonasal olfaction could not reflect the performance of flavoring substances by swallowing.
It is time to invent new instrument to identify retronasal substances.
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Malin Sandström Yes, it could. However, it is a kind of orthonasal flavor. Not really function to food and beverage, for which retronasal is more important.
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I have a student who interested in Olfactory Cognition. We want to make a comparison between the items on the VOIQ and the PSI-Q before we make a decision. I am struggling to get hold of the VOIQ or the original paper. An electronic copy of the below would be really helpful.
Gilbert, A. N., Crouch, M., & Kemp, S. E. (1998). Olfactory and visual mental imagery. Journal of Mental Imagery, 22(3-4), 137-146.
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Or of this:
Gilbert, A. N., Voss, M., & Kroll, J. J. (1997). Vividness of olfactory mental imagery: Correlations with sensory response and consumer behavior. Chemical Senses, 22, 686.
You may try to contact A. N. Gilbert or one of co-authors.
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In a patient with hereditary desminopathy (Thr341Pro DES mutation in a heterozygous state) with disease progression, a significant decrease in olfaction is noted. How can this fact be explained?
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I agree with Japneet Kaur. The problem in the cilia of olfactory sensory neurons. The myofibrilar myopathy is a genetic disease that associated with the primary ciliary dyskinesia. The primary ciliary dyskinesia resulted in defective cilia and olfactory receptors.
Attached, please find the article describing both myofibrilar myopathy and primary ciliary dyskinesia.
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What i mean is that if we are talking that the olfactory sensitivity of people is fluctuating due to different reasons (physiological state, mental state etc.), does it mean that the level of sensitivity is equal in case of all aroma compounds or it is possible that the sensitivity to some compounds /groups of compounds is lowers but to the others same time higher.
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Thank You Wender for you advise!
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I'm looking for literature relating insect detection of entomophagous fungi (olfaction/gustation) ... Sensory physiology or behaviour
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I sometimes believe that olfaction actually represents a basic form of affective processing. Has olfaction maybe always been the earliest form of an emotion system (evolutionary start of an emotion system)? Smelling things is so obviously and directly related to a "feeling" of pleasant or unpleasant, much more than it is related to "knowledge" about its origin (or semantic content).
The sense of olfaction has the most direct connections with the limbic system (e.g. amygdala) among all senses. Thus, neuroanatomy would strongly support this idea too.
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Typically, it is considered that olfaction is initiated by the interaction of odoriferous molecules with olfactory sensory receptors in the olfactory epithelium. It is entirely valid only for the naïve animal that never been exposed to the odorant, and the odorant has no visual image or sound presentations. For example, if dogs are trained to the certain odorants accompanied with optical or acoustic signals, or have inherited the knowledge of the odorant (like an odor of fire) the process of olfaction involves other modalities like vision, hearing, memory, thinking, analyzing, etc. These additional odor information processing associated with training and learning can be investigated if the olfaction can be evoked not by odorant molecules, but acoustic, visual, or memory impression of the odorant. The vocalization of “baked potato”, “rose” or “wood fire” evokes the perception of odors of these objects in the human. The visual images of the same objects make one to smell the same things. There is evidence that some odorants can modulate emotion and cognition. The piriform cortex and the amygdala both project to the orbitofrontal cortex that with the amygdala is involved in emotion and associative learning, and to the entorhinal/hippocampal system that is involved in long-term memory including episodic memory. Although, the entorhinal cortex collects and distributes information about olfactory memory and serves as a top-down modulator of olfactory cortical function. The medial and orbital parts of the frontal cortex are involved in the cognitive integration of all sensory stimuli in relation to prior experiences.
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Detection and recognition of smells
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The path from odorant to perception is quite complex. The initial events in olfaction take place in an olfactory neuroepithelium situated in the posterior nasal cavity. Olfaction begins with sniffing, that transports odorant molecules into the nose and delivers them to the mucus layer covering the olfactory epithelium. The binding of the odorant by a receptor protein initiates an intracellular cascade of signal transduction events, including the G-protein-dependent production of second messenger molecules, leading to opening of ion channels and passing of ion currents. This process triggers an action potential in the olfactory receptor neurons (ORNs) that projects directly to the olfactory bulb (OB). The signal is then transmitted to the anterior olfactory nucleus, piriform cortex, periamygdaloid cortex, and entorhinal cortex via olfactory stria. The signal at piriform cortex and periamygdaloid cortex is then sent to the thalamus and frontal cortex, where it is recognized and interpreted. The signal received at the entorhinal cortex projects to the hippocampus, where recognition memory of odors is processed. The anterior olfactory nucleus is involved in the processing of olfactory features and construction of representations (gestalts) for odorants. The correlations between olfactory gestalts are processed by the piriform cortex in association with frontal, entorhinal, and periamygdaloid areas. The periamygdaloid area is involved in processing the emotional information of the olfactory stimuli and memory encoding, whereas the entorhinal cortex collects and distributes information about olfactory memory and serves as a top-down modulator of olfactory cortical function. The medial and orbital parts of the frontal cortex are involved in cognitive integration of all sensory stimuli in relation to prior experiences. The thalamus’ role in olfaction is still controversial, whereas its involvement in odor thresholding and patterns of sniffing has been verified, at least in humans.
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I am looking to purchase an olfactometer similar to the one shown in the attached picture. Any help would be greatly appreciated.
Thanks!
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Back in the day, we would make our own small olfactometer systems. They have to be small for mites.  I would use polystyrene pill vials that can be cut by sawing with a metal-cutting (fine tooth) hacksaw blade, and glued together with superglue (to start) then sealed with 5 minute epoxy.  A sideways vibrating Dremel or Harbor Freight (cheap imported) vibrating saw ($14) with fine tooth blade will cut these vials nicely. Fine mesh of Stainless steel can be purchased from Grainger, or glue in plastic cloth mesh.  Nobody uses iron mesh anymore: Amazon and SIgma might not even have such an exotic material!
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If the neurotransmitters can promote chemotaxis they may bind to receptor over cell membrane of N. fowleri to stimulate them to move cephalhead.
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We have an old ATI Unicam 610 Series GC in our lab. This instrument is fitted with an olfactory port which is why I would like to "resurrect" the instrument. Unfortunately, the user manual is no longer with us.
I was hoping to connect the GC via its 9-pin "PL4 Datastation" port to a PC in order to record the basic data output, i.e. response vs. time. We do not need any form of integration as these samples have already been characterised on a GC-MS. We would simply like to be able to correlate the smell of eluting peaks with the GC-MS data.
Any suggestions on basic software that could record the output of the instrument is highly appreciated. Thanks to everyone in advance!
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It sounds like you desire something rather basic and inexpensive like the strip chart recorder, but able to display the peaks on the screen of the PC. If that is your desire, then I would suggest looking at any of the available 16 or 20-bit Analog Input Boards (PCI-e Interface) in a one or two channel format with basic software. Most of the general electronic catalog houses and supply houses offer these for general purpose use with a wide array of instrument types (sensors, thermistors, thermocouples, voltage outputs...) and depending on your software needs and channel resolution, the pricing reflects the complexity desired. If you just want a simple way to display an incoming analog signal between -0.100 mV's and + 2.000 volts DC (normal output of a GC), then a basic card and software should do the trick. Just be sure to select one that is compatible with your computer (interface card type), your detector output and has a high quality analog to digital input converter with enough resolution (16 or better yet 20 bits) to display mV signals accurately.
BTW: Companies such as National Instruments sell instrument interfaces and software of this type, but they are VERY expensive and based on the information you have provided, I do not think you need anything like that.
*Additionally, you will need to figure out which of the two wires on your existing DB9 chart recorder connector provide the output signal you need (should be easy if your chart recorder already works this way).
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Olfactometers allow for the systematic administration of odorants to humans. I'm looking for something similar (preferably commercially-available and computer-controlled) for tastes/liquids.  I've looked around, but so far, I haven't found anything.  I'm trying to avoid making my own if possible! :-)
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Hi Thomas,
Please check the link for the gustometers.
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I am looking to build my dissertation around the use of aroma's such as lavender, lemon balm, camomile etc in products around acute mental health wards to reduce instances of agitation in psychosis and behavioural disorders.
Any information would be gratefully accepted, thank you.
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Although it is not really within my scope of work, but I am not aware of any thorough recent review. There is rather a bit old generic pilot study from sussex suggesting possible positive influence on mental health, see below.
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The least weasel has suffered population decline in Switzerland over the past years. Due to its small body mass, presence / absence data is relativley hard to obtain. One method which has proven use full is the use of tracking tunnels.
But even if weasel presence is certain, the detectability of the species is low (i.e. the number of tracking nights needed per detection is high) . Baiting a tunnels with meat can raise the chances of detection, but at the same time attracts a high number of unwanted visitors making the tracking papers hard to impossible to interpret.
Least weasels have shown a strong preference for the odours of its selected prey, bank vole (Myodes glareolus) (link attached). Would it be possible to synthesize this odour to attract least weasels into tunnels? Can such an odour be synthesized?  Another option would be to use a weasel lure used by trappers (link attached). Does anybody have experience with this? Valeria tincture does not seem to have a significant effect on least weasels, or am I wrong?
Any help is appreciated!
EDIT: Thank you very much for taking the time to share your knowledge, you've offered some very helpful advice. In response to your questions:
@ Ole: Camera trapping has proved to be very difficult due to their small body size and the speed of their movement. We definitely want to test the newest camera traps on the marked to see how they fare with the least weasel, maybe we can design and experiment where we test lures and camera traps simultaneously. A closed enclosure with captive weasels would be the best way, since we have very little knowledge of weasel presence in our area.
@ Peter: Your approach to eliminate the odour sounds very reasonable. Again, we would need some captive weasels to test this. In response to the mechanic selection with body size: The “problematic” mammals who hamper the evaluation of footprints are mostly species of the same size or smaller: Rats, Mice and snails often invade the footprint tunnels, more so if meat is placed inside the tunnel to lure the weasels.
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In the Netherlands, Jeroen Mos developed the "mostela", which is a combination of a tracking tunnel and a camera trap. They had good results with this, and the movies also made it possible to individually recognise the weasels based on demarcation line and cheek spots (which was not possible for ermines). Of course also lots of movies of the prey species.
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Any troubles getting it working?
The flowmeter provided does not go over 160 ml/ min, which should be too low according to literature. Would the flow speed needed depend on the size of the olfactometer (current one - activity area diameter 30 cm)?
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Hi Sergey,
We got an answer form them that it should be fine to work with the olfactometer under the 160 ml/min range, but no more specifications. We will order new flowmeters and try to get it working, if still not then hopefully Toption can provide some help. Until then I was hoping to hear if anyone has been using successfully this instrument - maybe some publication with the exact system? 
Thanks for the reply :)
Rahel
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Do some odorants get internalized by the OSN, metabolized perhaps? Do some odorants just pop off each OR they activate and tumble into the next OR? Are there Odorant Binding Proteins shuttling odorants in reverse i.e. from OSN back into the mucous? What are typical odorant residence times on ORs?
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Dear Andreas,
It is very important for the insect to quickly degrade the odorant particle (miliseconds, perhaps?) in order to avoid a signal repetition, enabling it to perceive changes of the compounds concentration in the environment. For that, there is a specific class of enzymes called Odorant Degrading Enzymes (ODE) that are responsible for destroying odor particles after they are released from ORs.
A very good review about that subject can be found on the link below:
Kind regards,
Pedro.
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Kite patch are promoted as repellents rendering you "virtually invisible to mosquitoes".  They are based on the results of basic studies on mosquito olfaction suggesting that chemoreception can be blocked by particular chemicals.  A crown-founded campaign is financing field tests in Uganda.
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Dear Claudio (and Marcelo - both of you haven't changed at all, BTW!),
their facebook (https://www.facebook.com/kitepatch?fref=ts) and Indiegogo-page (https://www.indiegogo.com/projects/kite-patch#/updates) say that they performed what they call phase 1 in Uganda in April & May 2015. They are not going into what exactly they tested and how they did it, but it seems they also looked at possible attractive properties. Judging from their patent application (http://www.google.com/patents/WO2014028835A2?cl=en), these are probaly CO2-mimics.
I hope you are well, best wishes,
Andreas
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It is known that 1-2 nm zinc metal nanoparticles being added with odorant significantly enhance sense of smell.  We can speculate that zinc nanoparticles play the role of electron donors in the interaction with olfactory receptors (Turin L. A spectroscopic mechanism for primary olfactory reception. Chemical Senses. 1996;21(6):773-91). We see that only small nanoparticles, smaller than 4 nm are physiologically active.  Is there any physical rational for the size dependence? I guess, it should be a discrete dependence, not continues, as everything in a quantum physics.   Good reference?
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Thank you Nilmini,
I am interested the most in metal nanoparticles.
Vitaly
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I'm actively looking for a library of olfactory receptor. The goal is to have the broadest diversity. Do you have any idea about academic or commercial resources? Any advice for generating such library? Thank you. 
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Dominique- I am in private industry, am not allowed to publish, and so have no publications to view.  If I were in academia, it would be different, but this is the nature of the beast.  Our research is on insect olfaction.  We are looking at ORs, ORCOs and SNMPs all of whom, we reason, are involved in insect olfaction.  We are not interested in the genetic similarities as this has no bearing on our research.  Currently, we are interested in the physical properties of each of the three proteins.  You are welcome to email me, but I do not think I have much to offer someone with a background in immunology and antibodies.  Kindest regards, Tom
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We are exploring the possibility of collecting biopsies or exfoliates from the nasal mucosa. What is the best and more reliable methodology? Has anyone ever tested which of neural precursors lines from nasal mucosa or from iPSCs show higher concordance with the patient genome? 
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Dear Dr Depaulo,
Thank you for your answer and for the suggested references. It would be very useful to interact with Dr Sawa to exchange information and details.
I will defiantly give your regards to Maria.
 
Best regards,
Alessio
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Scent marking, integumentary glands, seasonal differences in scent marking, chemical communication in mammals
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Thank you all for your response on my doubt. I shall contact them.
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We want to produce PEX granule using Silane grafting method.However our final sample has an undesirable odor of silane. any idea how to reduce or totally eliminate that odor from the sample?
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Nima,
The very low concentration of ETBE in PEX will require a sensitive method like SPME/GC to measure.  I am not aware of methods to reduce ETBE formation.
Regards, Professor Dietrich
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We'd like to look at gene expression profiles in olfactory/nasal epithelium but have no experience in isolating this tissue correctly. We'd like to investigate this both histologically (RNA in situ and or immunohistochemistry) and by quantitative RT-PCR. Any help or advice would be greatly appreciated!  
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Respiratory epithelium is actually quite complex in rodents; it contains several different cells types, which vary according to the level and depth of the nasal cavity. To study histologically, usually you fix the whole skull by formalin immersion, then lightly decalcify, then tranverse slices are taken rostral to caudal and embedded separately. You can then make sections of each slice and stain for histology, IHC, or even use for in situ (with the usual caveats that ISH on formalin-fixed tissue can be a bit more difficult than on frozen). If there are specific areas of the nasal epithelium that you want to target and isolate, then you would do LCM (laser-capture microdissection) to remove those areas from sections, then do your PCR analyses on the removed tissue.
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how can i determine the taste detection threshold for difefrent compounds?
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please ,try the index R
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Coffee beans are used in perfume houses and sometimes left on counters selling fragrances (eg essential oils).
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I use it with my participants in aromatherapy and it helps.
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I found that gravid condition inhibits olfaction (need long time to give a response towards biopesticide odor). Can anyone provide me information to support this statement? Thank you so much
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Look for studies using the search term "physiological state" . That should help.
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It is known that enantiomers of some compounds can elicit different behavioral or olfactory responses in several species. I would like to know if such differences can be explained by triggering different transduction pathways. For instance, can one enantiomer trigger the adenylyl cyclase pathway and other enantiomer the inositol phosphate pathway in the same receptor?
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The end result of both pathways in OSNs is to open calcium channels, I'd be surprised if there was discrimination of enantiomers associated with either pathway. In addition, I've always understood that individual OSNs only have one type of messenger pathway. Therefore, if there is differential activation of secondary messenger pathways by enantiomers the activated pathway is not the source of the difference in reaction to the cue, but an indication of which class of OSNs reacts to the cue. 
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By associating olfactory cues to pain/no pain, drosophila and other animals can be trained to strongly avoid/prefer scents to which they were indifferent prior to training. Has anyone tried this with a "monoreceptor" animal, i.e. one where all but one olfactory receptor genes are knocked out? If you train using odorants known to be specific to the single remaining receptor the monoreceptor animal will likely behave no different than one with a full complement of receptors. What happens if one tried using odorant pairs that are known to NOT activate that receptor (e.g. in Ca++ influx or other assays). In other words, in the absence of other receptors, can training cause a receptor to expand its specificity to ligands it was previously "anosmic" to? We know point mutations tune a receptor's specificity, but what about post translational modifications or epigenetic changes effected by "training" of the molecule?
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Can the odorant specificity of an olfactory receptor be changed by associative training?
Odorants encountered in the environment help us find foods and avoid noxious substances. Successful food finding requires that perceived odors do no change from the first to the last encounter. The olfactory system is build under the guidance of genes, therefore mature olfactory receptor neurons (ORNs) in the olfactory epithelium are specialized olfactory neurons containing a single olfactory receptor protein. The specialized olfactory receptor protein binds the same odorants. Therefore the same olfactory receptor neurons (ORNs) during the repeated trials always carry the same information into the glomeruli of the olfactory bulb. The glomeruli are also specialized. In fish there are approximately a hundred different olfactory receptor proteins making a hundred specialized ORNs and a hundred different glomeruli in the olfactory bulb, in mammals the number of proteins and specialized cell types is closer to 1000 and approximately a 1000 types of olfactory glomeruli.
Specialized ORNs and specialized glomeruli enable that information entering the forebrain of fish or pyriform cortex of mammals is always the same. Olfactory percepts that are most probably formed there, in the third layer of the olfactory system must be stable during repeated conditioning sessions.  This is the condition sine qua non, which enables learning the conditioning stimulus, which enables that the same conditioning stimulus is always perceived as the same stimulus.
According to some investigators learning is located beyond the forebrain and according to other investigators in further layers of the pyriform cortex. Hypothalamus participates in learning the feeding stimuli.
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I have done tracksphere experiments of a pest caterpillar with Syntech Tracksphere LC 300. I have recorded the responses of the caterpillar towards 6 different plant leaf extracts, extracted in dichloromethane (uninfested and infested leaf extracts of 3 varieties). Five replicates were recorded for each extract, each time with a new caterpillar (separate recordings were done for dcm alone and for air). Can anyone please suggest a method for its statistical analysis?
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Because it is possible to measure many parameters from the 2D tracks that are recorded with Syntech tracksphere there is not a single response.The first point to consider is what kind of data you will extract from the raw tracks.
You  might be more interested in directionality, final vector length and vector angle,  or mean angles that  require circular statitstics.  But in case you need to compare two treatments that appears to show some attractivity, other parameters that measure a response "intensity" may be calculated directly or with R scripts working from the csv files: total walked distance, speed, both can be treated by standard statistics.  And you can also make distribution stats on the numbers of animals that for instance walk a minimal distance or show positive attraction. 
I agree with Sven that 5 replicates is far from enough.  Due to variability in insect behaviour, 30 replicates per treatment are recommandable. You can find examples of application in our paper Party et al  2013 PlosOne (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052897)
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I'm working on seal olfaction and did a PCA on a matrix of 220 scent compounds from 82 individuals. Is there a good way to figure out how many PCs may be relevant? I already did a scree plot and there are 3 'elbows' at PC´s 2,7,9. Also eigenvalues may be a criterion.
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Dear Martin,
As far as my field of study is concerned, we only consider the PCs with eigen values greater than 1.
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Why not some other number of TMs such as 3 or 5 or 9 which could still form binding pocket, have variable specificity, multiple activation modes etc. What's so magical about 7?
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An odd number allows N-terminal extra cellular and C-terminal intracellular (usually) and 7 helices permit the possibility to form a pore of ideal size for ions and small molecules.
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I have been looking for information indicating that humidity might be able to influence sensitivity and/or perceived odor quality in canine (mammal) olfaction. However I only found some correlations between canine detection probability of odor sources and humidity where humidity is (in my opinion) influencing the odor source and not the olfaction process. Does anyone know of any scientific reliable information that indicate that there is or is not an influence of olfaction by humidity?
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Dr. Downs - we observed this displacement of scent VOCs from soil by water and subsequent enhancement of analytical extractions (sample recoveries) from soil headspace. This 'flooding' effect is used to improve method detection limits for odorous VOCs from soil.
Wright, D., et al. 2005. Multidimensional GC-MS-olfactometry for identification and prioritization of malodors from confined animal feeding operations. Journal of Agricultural and Food Chemistry, (22), 8663-8672.
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By sampling headspace of plant volatiles by using PET oven bags we have sometimes measured contaminations by decanal and occasionally by different plant volatiles. Did you make similar experiences with such contaminations? We think the decanal is directly emitted by some charges of PET foil, while plant volatiles seem to penetrate the foil. This could be caused maybe due to quality differences of the product.
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I do not understand. What is PET? polyethylene terephthalate?
I guess so, sample with those bags always contaminate plants. In case you do volatile sampling is best done in glass, no phthalates but to a lesser extent. I have a glass jar for potted plants adapted to volatile plant foliage is sampled only and is not sampled the soil. Do you want me to send a photo?
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I am currently preparing a study that uses two odors, a pleasant one and an unpleasant one, as context cues, i.e., the odors will be dispensed in the experimental chamber and ss will perform a number of tasks. We have tried to match odor intensity by means of subjective intensity ratings on visual analog scales but the results were only partly satisfactory. In particular, different samples of ss (N=10 each) rated the intensity of the same concentration of the unpleasant odor significantly different while two different concentrations of the pleasant odor were rated different. Eventually the two odors were rated as iso-intense but I'm unhappy about how this aim was achieved. Any suggestions welcome.
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The main issue, as I see it, is conflating concentration of the odorant in the air with perceived intensity. One could easily have a chemical with a low concentration such as a mercaptan be rated as high intensity while vanillin at the same or at a higher concentration would be rated as very pleasant. The focus on matching concentration is misplaced. What you could do is have the subjects individually match the intensity of the pleasant and unpleasant odorant. I don't know if that would work in the context of your study. One should also consider the rate of adaptation as the study progresses. The unpleasant odor may not adapt at the same rate as the pleasant. It may not even adapt at all. More details of the study would be helpful.