Amyotrophic Lateral Sclerosis - Science topic

Embodiment is the idea that the brain does not need a detailed representation of the world, since the world is always present to organisms via an intact sensorimotor apparatus (Clark 1998). An extreme example of embodiment is the way in which the late Stephen Hawking (who suffered from the neurodegenerative disease amyotrophic lateral sclerosis, ALS) delivered his university lectures at Cambridge. Although he could communicate at only 0.1 bits per second [corrected for information redundancy, Reed and Durlach 1998] using a synthetic device (that was responsive to his cheek muscles, De Lange 2011) his lecture could be delivered at a normal rate of ~ 40 bits per second. Like most professors, his lecture would need to be prepared in advance. But in addition, the interface used by Hawking for communication was programmed with a word-prediction algorithm that had access to the entire lecture (Denman et al. 1997). Based on the characters initially uttered by Hawking, complete paragraphs could be summoned and delivered automatically through his voice synthesizer. Thus, there was no need for Hawking to memorize his lecture (which is also true for many of us who prepare slides in advance). In the absence of the algorithm, however, I am sure he would have had no problem communicating the contents of his lecture—but at a rate of 0.1 bits per second, which is far too slow for anyone to understand his speech. It is noteworthy that many people with Hawking’s condition pass away within several years of being overcome by ALS. For Hawking, it was his love of physics that kept him alive for his many decades of productive existence.

The importance of disease classification studies for the development of diagnosis & prognosis systems is crucial. Here the main problem is the lack of available medical datasets to use.

For EMG diagnosis, many studies used EMGLab datasets, but the website is NOT available currently.

And I can't find any open-access EMG diagnosis dataset. Parkinson's, SMA, ALS, or other. There are only hand gesture detection datasets present.

Other options are

1- Using an EMG simulation program like EMG-GAN (I don't know how efficient and representative it is)

2- Long-term clinical study with a budget

3- Somehow finding a -retrospective- signal record from a hospital (I don't know how to reach them)

Additionally, I want to know the usability of this short-term prototyping approach :

Simulation of signals by mimicking the patient movements, captured by sEMG device purchased. Can this, highly questionable and insufficient method, be used for the first analysis?

I want to hear your suggestions, thoughts, and shares about the topic :)

We know that the disease can be caused by different factors, one of which is environmental factors. Currently, we don't have much information about which they are and how they really influence in the development of the disease.

We know that this disease has no cure and those who suffer from it usually die 5 years after diagnosis. We want to know if the people who manage to live a little more than those 5 years is due to a specific treatment, if not, would that mean that it depends on each person?

I'm working on a project on speech recognition of ALS patients.

Hello!

I am analyzing the expression of different RNA molecules by qPCR in muscle and spinal cord of a mouse model of ALS and I am struggling because some of them gives are very variable between individuals. Consequently it is impossible to get significant differences between ALS and healthy animals, even though there is a very clear trend.

These specific RNA molecules are closely related to myogenesis, so we think they are very likely influenced by the animal's muscle mass. Unfortunately, when we collected the samples, we did not consider measuring the muscle mass of each animal; which would possibly greatly assist our analysis now. So, we would like to find any muscle mass indicator which could be used to normalize these data by qPCR.

Does anyone working in the field have any advice?

Thank you very much in advance.

Kind regards,

Tresa

I am developing the single tree detection method from ALS point clouds. To test the robustness of our proposed method, I need more ALS datasets for experimental analysis. The datasets should own referenced single tree extraction results, such as the (X, Y) coordinates of the tree tops. In so doing, we can conduct quantitative analysis and make comparison. Can anyone provide me some Forestry ALS Datasets for testing single tree detection rate?

Thanks a lot.

Hello there!

I have searched everywhere for a MRI dataset for amyotrophic lateral sclerosis, ideally a multimodal one (DTI especially would be appreciated).

Thank you in advance.

where can I found free Airborne Laser Scanning (ALS) data?

M group has worked on the gene database of AD, PD, SZ, SZ and ALS. I wonder if there is any gene database compiled for hypertension, diabetes, or other comorbidities. Please let me know.

An example of the analysis is available at:

This is a potentially important piece of work that sets the lives of patients with ALS within a broader context than the progressive loss of function. It fits with the work of others (including me) who have long argued for understanding patient needs and care within their changing perceptions of life and self. Alas, the work has yet to be translated but I can hope that, in the future, an English version will be available.

Tom Koch

Alton Medical Centre

Toronto, Canada.

I'm aiming to use an adoptive cell transfer approach, with microglia in mice with ALS. So far all the protocols I have seen, require sacrificing the mouse. I'd like to re-infuse the microglia back into the same original mouse, once I've over expressed a receptor using lentivirus transduction.

I am looking for an explication of ALSAQ-40 and ALSFRS-R questionnaire because I dont´find how is the final assessment of this scale? That is to say, how can I know which are outcomes of scales and its interpretations? I am searching for literature that gives the degrees of the scale as outcome. 

Research has shown that mitochondria protecting agents could offer theraputic benefits in ALS. I am looking for suggestions on which ones, already used in humans, would be good candidates for further research?

I have forestTLS and ALS point clouds data now. What I want is to reconstruct the three-dimension forest,including terrain, trees, shrublands and grass. I wonder if I need to classify these categories first and how to classify. And how to realize the reconstruction.

We are trying to get literature on race determination of ALS of tobacco and we want to have an idea of inoculation methods and optimum conditions for ALS. We have not managed to establish ALS infection on tobacco for more than 5 years now.

Dear everyone!

I work on EMG control and EMG interfaces for bionic (myoelectric) extremity reconstruction. I have a relative with ALS and was wondering if anyone has experience in controlling a computer mouse or wheelchair with EMG?

The scientific literature is almost empty. I have found only one case report.

Glad if anyone has some ideas.

Thank you

Hi,

During developement of GC-FID ALS method for quantification of Methanol, IPA, ACN, DCM and DMF I am observing blank interference in methanol, IPA and ACN peak due to DMSO (I came to know its DMSO after doing truobleshooting). I am using DB-624 (75m, 0.530mm, 3.2 um ) column with flow of 2.5 mL/min, my inlet temp is 170 degree celcius and detector temperature is 280 degree celcius. Split ratio is 1:4. I have used different make DMSO but none helped me. Kindly note my sample has solubility in only DMSO so i can not move to different diluent. Please help me.

Regards Ankit

I am developing an assistive communication switch for people with communication disabilities, & for IT control, using voluntary contraction of the tensor tympani muscle of the middle ear. An otoscope camera records the voluntary movement of the drum, and movement detection software triggers the Grid3 assistive technology software. I have proven the concept, but looking for research/ development funding it would be useful to have some idea of prevalence. There are a few series in the literature (eg from Professor Bance) showing upto 8 individuals but no prevalence studies. Is anyone aware of any more information? And for a less scientific indication; do you know if you have TT control?

It would be great to get some preliminary indication of whether this is a rare phenomenon, if you would be willing to complete the survey please? https://www.surveymonkey.com/r/VHZYV9D

Thanks very much for your help and advice

Nick Gompertz

Hi Everyone,

I am working on ALS disease. We are interested to see total protein expression and the phosphorylation status by mass spectrometric approach. I have go through some articles, in which they used lumbar spinal cord or other spinal segment in case of interest other than ALS disease. My question is, whether or not its feasible if i take ventral horn region from lumbar spinal cord, Just like if the ventral horn has to be cut from the central canal region under the presence of stereo microscope. So, how it has to be considered, i am wondering if i cut the tissue from the centraI region, whether would it have any effect on ventral horn region in further mass spec analysis. Or should i simply proceed the lumbar spinal cord region. I was thinking for the ventral horn region position in a context of its significance in ALS.

Comments will be highly appreciated!

Thanks

Best,

Shabbir

I try to stain the Acetylcholinesterase and the Cholin-acetyltransferase in neuromuscular junction of diaphragm of mice with ALS model. I use abcam antybodies - Anti-Acetylcholinesterase antibody [HR2] ab2803 and Anti-Choline Acetyltransferase ab34419, I use standart IF protocol.

How to stain these enzymes in NMJ for IF method? Has anybody stained it?

i have a clinical trial of injecting MSCs for ALS patients the results of the MRI were increasing in spinal cord diameters.

So im wondering about the correlation between ALS and spinal cord diameters change and is increasing spinal cord diameters is a good indication and why ?

The objective is to reproduce an in vitro-model of ALS.

Thank you

im doing a systematic review for ALS treatment with MSC and all the clinical trials are single arm, so i was wondering how to do meta analysis on it

Hi!

I am looking at cortical neurons in coronal sections from mice expressing Thy-YFP and a top secret genetic manipulation :)

I noticed these vacuoles in the apical dendrites of most of the neurons, and was wondering if anyone with an experienced eye can tell me if these look like some sort of artifact? The brains were perfused, fixed, sunk in sucrose, frozen, and sectioned on a microtome. Ice crystals? Freeze thaw damage?

I don't have a wildtype to compare it to right this second due to technical difficulties, but am impatient and thought I'd ask all of you first, ESPECIALLY because of what I found out when I googled apical dendrite vacuoles. Thanks!

Sara

hi all,

I'm looking at the ALS guidelines from around the world, but need them from the following countries if possible. a pic is absolutely fine

Qatar 2000-2015 if possible

Pakistan 2000-2015 if possible

I know you amazing minds will either remember them or have them, or will know where I can find them

its for a paper I'm currently writing. I'm also looking for if possible someone in Pakistan (paramedic or dr) preferably who can answer a few questions if possible.

many thanks

Hi everyone :)

I am a second year biomedical sciences bachelors student and I don't have a lot of experience. I've searched the internet to anwser my question but I can't find it. We want to increase cytoplasmatic catalase expression (since overexpression of cytoplasmatic catalase best provides protection against H2O2) in motor neuron-like hybride cells and see how it affects ferroptosis. We are using NSC-34 hybride G93A cells as a model for ALS. How can I overexpress cytoplasmatic catalase in hybride NSC-34 cells?

ALS patients use to get swallonwing disorders related lung infection and as physiotherapist, i'am short in tools to help them to improve their swallowing ability nor caughing ability.

Could anyone share experiences or protocole ?

Thanks yo for your concern

Seif

For elucidating the molecular mechanisms of these neurodegenerative diseases, study of transgenic mice models is a must.

Hi everyone,

I have some questions regarding astrocytes morphology, primary culture, and MBP expression pattern. I am new in the field of neuroscience.

I am working on knockin mice of ALS model.

I dissected 8 months old mutant mice, and lumbar spinal cord showed increased astrocytes signals as compared to age matched WT mice. I crossed check with iba1 (Microglial activation marker) that supports the case.

At the same time, i did dissection of 9 months old (3 mice), in which we observed significant reduction of astrocytes in mutant mice mostly at peripheral region of spinal cord and +ve caspase signals as well. However the ventral region of lumbar spinal cord in 9 months mutant mice also reduced and it seems their morphology is compromised as well. It might be reactive astrocytes.

Now i wanted to do primary culture and to see the effect of this mutation on motor neurons and glial cells.

My question is, whether or not i can see the effect of this mutation in primary culture, if its phenotype comes around 9 months.

And can we see some radial glial cells in 9 months old mice if we stain with GFAP, as mostly we corelate GFAP with astrocytes in adult mice. Regarding MBP pattern, i am thinking that it should be at the peripheral region like it has the particular boundary between ventral and periphery. Or its pattern is at the extreme periphery appearing as a layer.

And finally if someone has a protocol for spinal cord primary culture.

It would be highly appreciated.

Thanks in advance.

Regards

shabbir

Concepts on IL-10, low dose specific immunotherapy (SIT) etc 

PubPeer:                                                                                    May 29, 2017

Unregistered Submission:

(May 25th, 2017 2:46 am UTC)

In this review the authors attempted to estimate the information generated by neural signals used in different Brain Machine Interface (BMI) studies to compare performances. It seems that the authors have neglected critical assumptions of the estimation technique they used, a mistake that, if confirmed, completely invalidates the results of the main point of their article, compromising their conclusions.

Figure 1 legend states that the bits per trial from 26 BMI studies were estimated using Wolpaw’s information transfer rate method (ITR), an approximation of Shannon’s full mutual information channel theory, with the following expression:

Bits/trial = log2N + P log2P + (1-P) log2[(1-P)/(N-1)]

where N is the number of possible choices (the number of targets in a center-out task as used by the authors) and P is the probability that the desired choice will be selected (used as percent of correct trials by the authors). The estimated bits per trial and bits per second of the 26 studies are shown in Table 1 and represented as histograms in Figure 1C and 1D respectively.

Wolpaw’s approximation used by the authors is valid only if several strict assumptions are true: i) BMI are memoryless and stable discrete transmission channels, ii) all the output commands are equally likely to be selected, iii) P is the same for all choices, and the error is equally distributed among all remaining choices (Wolpaw et al., 1998, Yuan et al, 2013; Thompson et al., 2014). The violation of the assumptions of Wolpaw’s approximation leads to incorrect ITR estimations (Yuan et al, 2013). Because BMI systems typically do not fulfill several of these assumptions, particularly those of uniform selection probability and uniform classification error distribution, researchers are encouraged to be careful in reporting ITR, especially when they are using ITR for comparisons between different BMI systems (Thompson et al. 2014). Yet, Tehovnik et al. 2013 failed in reporting whether the assumptions for Wolpaw’s approximation were true or not for the 26 studies they used. Such omission invalidates their estimations. Additionally, the inspection of the original studies reveals the authors failed at the fundamental aspect of understanding and interpreting the tasks used in some of them. This failure led to incorrect input values for their estimations in at least 2 studies.

The validity of the estimated bits/trial and bits/second presented in Figure 1 and Table 1 is crucial to the credibility of the main conclusions of the review. If these estimations are incorrect, as they seem to be, it would invalidate the main claim of the review, which is the low performance of BMI systems. It will also raise doubts on the remaining points argued by the authors, making their claims substantially weaker. Another review published by the same group (Tehovnik and Chen 2015), which used the estimations from the current one, would be also compromised in its conclusions. In summary, for this review to be considered, the authors must include the ways in which the analyzed BMI studies violate or not the ITR assumptions.

References

Tehovnik EJ, Woods LC, Slocum WM (2013) Transfer of information by BMI. Neuroscience 255:134–46.

Shannon C E and Weaver W (1964) The Mathematical Theory of Communication (Urbana, IL: University of Illinois Press).

Wolpaw J R, Ramoser H, McFarland DJ, Pfurtscheller G (1998) EEG-based communication: improved accuracy by response verification IEEE Trans. Rehabil. Eng. 6:326–33.

Thompson DE, Quitadamo LR, Mainardi L, Laghari KU, Gao S, Kindermans PJ, Simeral JD, Fazel-Rezai R, Matteucci M, Falk TH, Bianchi L, Chestek CA, Huggins JE (2014) Performance measurement for brain-computer or brain-machine interfaces: a tutorial. J. Neural Eng. 11(3):035001.

Yuan P, Gao X, Allison B, Wang Y, Bin G, Gao S (2013) A study of the existing problems of estimating the information transfer rate in online brain–computer interfaces.  J. Neural Eng. 10:026014.

Through published articles as well as the lead researcher of the study that "birthed" the trial.. there should be a phase 1 trial of Necrostatin -1/Necrostatin1S analog either in-progress or done.

*****

"Our study suggests that blocking RIPK1 might work in human ALS patients as well. A Phase I human clinical trial will soon start in Denali Therapeutics to begin to test this hypothesis," Yuan added.

In Dec of 2016 I exchanged emails with Dr Yuan and she states the trial is underway and "so far so good" and later stated it was taking place in the Netherlands. It might be run by Incron Pharma (as they were bought by Denali)

It's not popping up anywhere and the Dir of Projects at Denali is saying "I have the wrong person" when I ask her where the trial stands.

Wouldn't a trial have to register with either a specific country or some agency.. or is it totally private until a certain stage?

Thank you,

Todd Batt

I have been looking more closely at the reduction of defensin 5 alpha reported by Wu et al in the ALS mouse model as to me, the leaky gut is the first notable symptom for ALS and it occurs ahead of neurological symptoms.  My self selecting question about whether or not people had gut issues ahead of ALS found that 60% of respondents said they had gut issues ahead, and for years by some of them.  So, given that the lack of defensin 5 alpha is causing a shift away from butyrate forming microbiota to a more harmful one and a reduced protection from intestinal barrier which causes a huge range of other problems, figuring out how to help the body make defensin 5 alpha seems like a good strategy for fighting back.

So, what can help the body make defensin 5 alpha?  Anyone have any sources for doing that?

Wu, Shaoping, et al. "Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse model." Physiological reports 3.4 (2015): e12356.

Ghosh, Dipankar, et al. "Paneth cell trypsin is the processing enzyme for human defensin-5." Nature immunology 3.6 (2002): 583-590.

Wang, Wei, et al. "Effect of bifidobacterium on defensin-5 expression in intestinal injury of preweaning rats." World journal of gastroenterology: WJG 21.9 (2015): 2638.

Hetz, Claudio, et al. "XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy." Genes & development 23.19 (2009): 2294-2306.  (my note - helps the paneth cells, I think)

Courth, Lioba F., et al. "Crohn's disease-derived monocytes fail to induce Paneth cell defensins." Proceedings of the National Academy of Sciences 112.45 (2015): 14000-14005.

Kaser, Arthur, et al. "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease." Cell 134.5 (2008): 743-756.

ex each word has diff character but 1 character can 1 vector representation like 15 dim but when a word is represented in terms of characters

w1=[c1,c2,c3,c4]=[[…..15] [….15][…..15][….15]]

w2=[c2,c3,c5] =[[…..15][….15][…..15]] How can these different representation be combined into fixed length vectors

I am trying to figure out

This source, http://www.wetwebmedia.com/ca/volume_6/volume_6_1/thiaminase.htm, says that "There is not just one type of thiaminase, but several different ones, some of which can be produced by bacteria, fungi, plants and potentially animals."

I am particularly interested in bacterial and fungal sources.

I am also looking for studies on Clostridium sporogenes in people, and if  Bacillus aneurinolyticus has been found in people.

Another question, when people get fevers I tend to think of it as the average body temperature has increased, but I am wondering if anyone knows of any studies showing specifically that perhaps the body does something local that causes a very localized temperature spike and then that energy dissipates to give us the average temperature we measure on a thermometer.

My search efforts are not getting very far so if anyone can steer me where I might look for these answers I would be most appreciative.

Thanks.

I am working on Amyotrophic lateral sclerosis and try to amplify the GGGGCC hexanucleotide repeat expansion on Chromosome 9 (C9ORF72). I amplified it with FAM labelled primers by repeat primed PCR and ran the product on sequencer, but I did not get exactly six nucleotide differences between peaks. I also have done normal PCR with outer primers and got smaller sized products. Please help me out if anyone is working with repeat primed PCR Thanks.

C9orf72 is an expansion related to some neurological diseases such as ALS or dementia.

Hello everyone,

I've stained for astrocytes in the human brainstem. Attached is an image I took from the fluorescence microscope. The cell density is too high, I'm wondering whether it'll be possible to count the number of astrocytes using Fiji/ImageJ.

In diseases like Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis misfolded proteins are implicated heavily in the course of disease progression (e.g. Tau, alpha-Synuclein, SOD1 respectively). It seems like these misfolded proteins are especially neuro-toxic since nuerons are ill-equipped to handle the aggregates as more misfolded protein accumulates. But why is it that the misfolded proteins seem to specifically target wild-type forms of the same protein. misfolded-Tau templates wt-Tau, misfolded-Alpha-synuclein templates wt-Alpha-synuclein, and misfolded-SOD1 templates wt-SOD1. What is the mechanism of specificity for prion-like templating? Couldn't the misfolded proteins disrupt non-self wild-type proteins to induce aggregates? Does this occur?

I have visited an 29-year old man from Mali with signs of lower motoneurons (bulbar, upper limbs), resembling ALS. He travelled for 8 months from Mali to Italy in extremely hard conditions. Does someone know whether there are some toxic or infectious agents that can mimic ALS?

Thank You

I have limited experience with the treatment of 2 patients with ALS,

After establishing a breeding colony utilizing several transgenic males (B6.Cg-Tg(SOD1*G37R)29 Dpr/J aka Line 29) and C56BL/6 females from a commercial source, we noticed that the generated progeny expressed a significant delay in phenotype onset. Typically these animals exhibit an 8-10 months lifespan, but the cohorts in our study survived much longer (transgenic +ve males: median lifespan 600d, transgenic +ve females: 560d). At the outset, male breeders were genotyped (qPCR) by Jackson prior to arrival at our facility. Similarly, at weaning, qPCR analysis was performed to identify transgene positive progeny. The qPCR data indicated that the genomic signatures for all the progeny animals were rather closely clustered, but quite diminished from animals that we had previously derived from a collaborator’s line 29 breeders. Since the dCt values for progeny between breeding pairs were not significantly different, it is highly unlikely that recombination events had resulted in a loss of hSOD1 transgene copies during the 3 breeding cycles that we had performed. At this point, it appears that the most plausible explanation is that transgene copy loss had occurred between the time the animals were deposited at Jackson Laboratory, and by the point that we had obtained these animals for use in deriving our colony. That said, does anyone have any insight with respect to the frequency of transgene instability in the G37R model, or transgenic animal models in general? My survey of the literature has indicated that in the G93A model, this occurs rather infrequently (transgene loss is approximately 3%). I have no reason to believe that it would be more frequent than this, but up until this point, my search has been quite unfruitful.

We have a transgenic KO mouse model for ALS and are wanting to look at mitochondria as a possible indicator of retrograde transport disruption in motor neurons. We have longitudionally sectioned muscle tissue to use for the preliminary work that we normally use to look at the neuromuscular junction. All of the literature I've been able to find is either about mitochondria in the neurons, or in the muscle but nothing about the junction.

Any suggestions would be greatly appreciated.

We are a medicinal chemistry group. In the last period we synthesised a small library of bioactive compounds with a various range of structures (mainly designed as cholinergic molecules) and we are looking for a group willing to evaluate their binding affinity at different biological targets (to identify a lead compound) and/or to discover if they have any pharmacological activity on animal models of disease. This would be the starting point of a new scientific collaboration. If interested please contact me.

I believe that all therapy have yielded good results on SOD1 mouse did not work (or little) in clinical trials in humans. TDP-43 mutant transgenic mice seems to develop features of ALS but it will die of intestinal occlusion and does not express the progressive muscular degeneration of ALS. What the best model, or combination of models for study effect of a therapy?

Hello, I'm currently writing a literature based dissertation project about Amyotrophic Lateral Sclerosis and therapeutic drugs required for its treatment. Therefore I was hoping if there would be any clinical trial data information available..? Thanks

There is not very exact information regarding whether stem-cell therapy is useful for patient with amyotrophic lateral sclerosis.

SOD is known to interact with other proteins known to cause familial ALS, does this make the framework destabilization of SOD a priority target for interventions? What are the other promising targets?