(or “Catch me (Cd2+) if you can”)

The objects of the entire 1st experiment of this series of posts are MKPs (MAP kinase phosphatases).

The subject is possible mechanisms cadmium could “use” to influence MKPs (and thus MAPK signalling pathway).

The purpose of the 1st experiment is to leverage some bioinformatics tools to find those possible mechanisms.

Let’s try to carry out MSA (multiple sequence alignment) of MKPs, namely DUSP1.

We are going to use Clustal Omega tool to do it [1].

Proteins, DNAs and RNAs are polymers consisting of repeated monomers.

MSA is an alignment of those sequences.

And the alignment is the process of finding similarities between different sequences.

In a nutshell, this tool is just provided (by us) with sequences (in our case protein sequences) and then it analyses them and tries to find identical (or similar) monomers presented in provided sequences.

(if this concept is new for you, then probably it would be much clear when you look at the image near the bottom of the post)

You can use this tool for example

1. to make a beautiful illustration for your article. Let’s say that you know what residues you are looking for (and you know that they are conservative (so that actually you could even do that alignment by hand)), but this tool helps you to present that information in an easy-to-understand less time-consuming way.

2. to compare sequences of a particular protein of different organisms to try to figure out if there’s something conservative there. And if there is (if there are some identical (or similar) residues there), then you can assume that those motifs/regions are responsible for some important functions (structure defines functions) and probably represent a protein domain/motif. And then analyse those proteins more carefully.

As we mentioned in the previous post, Cys residue is responsible for catalytic activity of phosphatases [2].

Usually catalytic motif ((V)-HC-XX-X-XX-R-(S/T) in our case) is highly conservative among different organisms. So, it should not be a surprise that we will see all those Cys residues of DUSPs aligned in 1 column in different organisms.

What would be interesting to see (for the purposes of our experiment) is if there’re some other conservative Cys residues in those proteins.

Aside from catalytic centre, enzymes also have some sites for other molecules to regulate their activity (allosteric site/regulatory site). In the case of this series of posts (where we are discussing MKPs) those Cys residues will be very important, because Cd+2 possibly indirectly could influence MKPs activity through those Cys residues. (we will discuss this in the next posts, and this possible “indirect” effect is in the main focus of the 1st Exp.).

So, let’s try to align DUSP 1 sequences of different organisms and see if there are any conservative Cys residues (except for Cys of catalytic site) there.

First of all, we need to get those sequences. For that we’ll use UniProt.

UniProt (Universal Protein Resource) is the central place for us to get proteins sequences and information about them [3].

We’re going to analyse DUSP1 because searching for other MKPs gives us just 1-2 DUSPs entries (and searching for DUSP1 gives 5 entries). Just search for “DUSP1” in the search box and you'll see

the entries. Then choose in “Filter by” filter (on the left) “Reviewed” option. This removes “Unreviewed” entries. As a result we get only entries annotated (documented) by experts (rather than automatically generated annotations (for more information on this go to https://www.uniprot.org/help/about)).

(screenshot was taken from Uniprot)

There're 68 results. And we get a lot of entries of proteins which are not actually DUSPs, but somehow relate to them. We need only DUSPs, so we’ll choose the first 4 entries (4th and 5th entries are almost identical (and belong to one organism), so we’ll use just one of these (with Q91790 entry identifier)).

We have the sequences of 4 organisms (Xenopus laevis (Amphibians) and Homo sapiens, Mus musculus, Rattus norvegicus (Mammals)).

Click the “Column” option to get rid of some unnecessary columns (leave only “Length”, “Organism”, “Entry name”, “Gene name”, “Protein names”).

(screenshot was taken from Uniprot)

Click save at the bottom of the modal window. Then choose/check the first 4 entries and download them in ‘FASTA (canonical)’ format with the help of “Download” option.

(screenshot was taken from Uniprot)

The file with results should look like

(the image was created by me with Notepad/Paint, and you can use it if you want. Sequences were obtained from UniProt)

|| Useful tip

FASTA format is a text format used for DNA/RNA/protein sequences representation.

*Aside from sequences themselves it also might contain kind of meta-information (at the beginning) such as UniProt identifier, species name, full proteins name etc. [4]. This is similar to when we use Markdown at Steemit (it also contains some meta-information, aside from text itself).*

(This is the molecule in complex with its substrate (a piece of the cell wall of bacterium (N-acetylmuramic acid (highlighted in blue) and N-acetyl-D-glucosamine (highlighted in sky blue)). Cartoon representation. The image was created by me with the help of PyMol - open source tool for molecular visualization/exploration. PDB-file was obtained from PDB)

Lysozyme was discovered accidentally near 100 years ago by Sir Alexander Fleming (the scientist known for his discovery of penicillin (1928)) in 1921. It happened accidentally, when a drop from his nose fell onto an agar plate with some microbes. He concluded that the drop contained a lytic substance, when he saw that the microbes were fading. Thus, he discovered antimicrobial properties of lysozyme.

It was the first antibiotic discovered [1].

Discovery of lysozyme was so important, that there medals and sculpture/s dedicated to this molecule.

Sculpture

“Tears” sculpture was created by Mike Tyka in 2015.

Bronze part represents the carbohydrates of the bacteria cell wall. Lead glass part represents lysozyme [4].

(image was taken from http://www.miketyka.com)

Discovery of the atom structure led to the first detailed enzymatic mechanism to be described and was a major breakthrough in our understanding of how our bodies' metabolic functions

[4].

The Fleming-Lysozyme Medal

(Images were taken from “Lysozyme.” book [3])

This medal was created to commemorate the fiftieth anniversary of the discovery of lysozyme by Sir Alexander Fleming and to mark the occasion of the Lysozyme Conference held at Arden House, Harriman, New York, October 29-31, 1972.

On the obverse side of the medal we can see Sir Alexander Fleming.

On the right of this side are M. lysodeikticus (known today as Micrococcus luteus) (untreated bacteria (upper field) and treated with lysozyme bacteria (lower field)).

On the left we can see “Chance favors the prepared mind” dictum (given initially by Louis Pasteur).

On the reverse side of the medal is a culture plate with M. lysodeikticus. At the centre of it is a zone with Fleming‘s tears (which led to bacterial lysis).

The labeling of “M. lysodeikticus” and “lysozyme (tears)” is in Fleming's own hand.

[source – [3]]

Above that plate you can see part (active site) of the 3-D structure of hen egg-white lysozyme.

as defined by the X-ray crystallographic studies of David Phillips and his associates. The four circles represent the oxygens of the aspartic 52 and glutamic 35 residues which specifically accomplish the hydrolytic cleavage of the lysozyme substrate.

[source – [3]]

The medal was created by Abram Belskie [3].

Lysozyme is an enzyme, also known as muramidase or N-acetylmuramide glycanhydrolase, because it helps to break (1->4)-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycans. [9]

In other words, lysozyme helps to break the cell wall of bacteria, which leads to their death.

Among other names of this molecule are N,O-diacetylmuramidase, L-7001, PR1-lysozyme, globulin G, globulin G1, mucopeptide N-acetylmuramoylhydrolase, mucopeptide glucohydrolase, muramidase [12].

Lysozyme belongs to glycoside hydrolases class of enzymes. In a nutshell, it means that it is an example of enzymes which help to break complex sugars by using water molecules.

It has been shown that the key amino acids responsible for enzymatic activity of lysozyme in chicken egg white are glutamic acid 35 (Glu35) and aspartate 52 (Asp52) (where the number represents the position of amino acid in the polypeptide chain) (remember that medal above). It’s this pair of amino acids, which uses the water molecules to split the sugar [14].

What you see on the first image of this post is the lysozyme of Escherichia virus T4 (that bacteriophage which infects Escherichia coli).

Analogues residues to glutamic acid 35 (Glu35) and aspartate 52 (Asp52) of egg white in this case are glutamic acid 11 (E11) and aspartate 20 (D20) (highlighted in hotpink). They help to break the linkage between N-acetylmuramic acid (highlighted in blue) and N-acetyl-D-glucosamine (highlighted in sky blue) [13].

They suppose that the origin of lysozyme goes back approximately 400 to 600 million years [15].

Lysozyme is the first protein, which was found to have all the 20 usual amino acids, it is the first enzyme to have its mechanism of action revealed, and it’s the first enzyme for which scientists solved its 3D-structure (with the help of X-ray diffraction methods). It’s a small and stable enzyme.

(This is the molecule in complex with its substrate (a piece of the cell wall of bacterium (2 sugar rings) (highlighted in marine blue)). Cartoon representation. The image was created by me with the help of PyMol – open source tool for molecular visualization/exploration. PDB-file was obtained from PDB)

All that makes lysozyme an ideal candidate for research of protein structure / function. That’s why Brian Matthews (University of Oregon) used this protein to study functional changes of proteins due to structural changes (creating new active sites, removing large residues inside the protein etc.). He created so many mutants of lysozyme, that it became the most common protein in the PDB [8].

(This is the molecule in complex with its substrate (a piece of the cell wall of bacterium (2 sugar rings) (highlighted in marine blue)). Surface representation. The image was created by me with the help of PyMol – open source tool for molecular visualization/exploration. PDB-file was obtained from PDB)

This contest is an attempt to promote scientific knowledge among community in a fun and interesting way with the help of molecules.

Some people like to travel around the world and tell others stories about what happens outside of our organisms/cells in other countries.

And with “Identify the molecule” contest you can try to travel inside our own organism/cells and cells of the organisms around us.

For more information about this contest read “Identify the molecule” league. Prize: knowledge + 5/10 XRP + 200/400 TMN post.

Prizes/bonuses:

The prize here is

1. knowledge

facts, information, and skills acquired through experience or education; the theoretical or practical understanding of a subject

[Oxford Dictionary of English, 3rd Edition, Oxford University Press, 2010]

That understanding of our own organism and organisms around us is the real prize in the case of this contest. No matter what happens (whether or not you get 5 XRP), you can win (can acquire the knowledge by investigating different sources of information, remembering and using it to your advantage in the future).

2. 5 XRP

3. 200 TMN

Aside from XRP I’d like to add TMN tokens.

For the uninitiated, TMN is the token of TranslateMe project (it’s about combining blockchain technology (NEO in this case) with translation industry).

The reason I’m going to add this token for the prize pool of this contest is not only because I have them, but because this contest is quite scientific, and TranslateMe project might help to solve the “lost” science problem.

For more on this you can read my post regarding TranslateMe (TranslateMe (or Decentralization meets Translation industry). Part 2. The “missing puzzle piece” of scientific ecosystem. General overview) (and other posts of that series).

For more information on crypto-bonuses for this league, please refer to “Identify the molecule” league. Prize: knowledge + 5/10 XRP + 200/400 TMN post.

Consider these tokens as a bonus.

Images and text are the clues for you to guess a riddle (the name of the molecule in this case).

Note that

a) even though this contest is called “Identify the molecule”,

-> molecule (singular)

sometimes it’s not just a molecule which is responsible for a specific function, but rather a complex of molecules.

Example:

cytochrome c oxidase (Complex IV)

is a large transmembrane protein complex… It is the last enzyme in the respiratory electron transport chain of cells located in the membrane.

source

b) some molecules/complexes have different names. For example, other names for cytochrome c oxidase (example above) are

Complex IV (mitochondrial electron transport). Cytochrome a3. Cytochrome aa3. Cytochrome oxidase. Warburg's respiratory enzyme.

source

Any of those names would be a valid entry.

c) Some almost identical molecules are grouped into classes / groups / families.

Example:

Helicases are divided into 6 groups. RecD and Dda molecules belong to helicases group (Superfamily 1 (SF1)). In this case you would need to guess only the name of the group –> Helicase/ Helicases.

d) Some proteins can have different forms – isoforms.

Example:

There’re trypsin 1 and trypsin 2. In this case you would need to guess only the general name – trypsin.

Important

In order to get TMN, you’ll need to have NEO-wallet and provide me your public NEO-address.

If you don’t have it yet, don’t worry, I published a post on how/where to get it (O3 wallet).

Note that NEO-addresses provided by exchanges will not work in this case (+ it's safer NOT to keep your funds on exchanges). It's highly recommended to get O3 wallet.

If there’re no winners on any stage, the prize will be distributed equally among all users who provided any guesses for molecules.

Rules

This contest lasts for 6 days.

Given that I don't see a comments section on Coil, I set up a Telegram group for this league, so that you could leave your reply with the guess there.

Leave your guess (1 guess only) in the Telegram group.

Don’t edit your comment/reply and don’t provide any evidence that your answer is correct.

The first user with the right answer is the winner.

I’ll provide the answer in the Telegram group.

Some of the clues have already been provided in the post.

Additional clues will be given in 2 days (on Monday, February 3, 2020, 20:00 ± 2 minutes UTC) (I’ll update this post).

And the rest of the clues will be provided in 2 more days (on Wednesday, February 5, 2020, 20:00 ± 2 minutes UTC) (I’ll update this post).

The reason is that some people might need less information to make conclusions that the others.

Additional clues will be added at the end of the “Riddle” section before the “Rules” section with “Edited” label.

The winner will be announced in that group (+ I'll publish a detailed review of the riddle after a while) on Friday, February 7, 2020, 20:00 ± 5 minutes UTC, so it's recommended to check that group on the 6th day.

I'll ask to provide me there your XPR-address.

I’ll transfer the tokens (XRP + TMN) (if the winner provides me his/her NEO-address) to the winner on that day (February 7) and add the transaction ID in the Telegram group.

I’m planning to run this contest every week.

So, you should expect to see the 2nd week’s riddle for January on Saturday, February 8, 2019, 20:00 ± 2 minutes UTC.

The riddle goes below.

In this series of posts I'm going to discuss the potential of the blockchain + science union.

(cover image source (Scientific Coin video on YouTube))

I’m just an amateur scientist.

To my knowledge, there’re 4 main problems in today’s science:

1. Access to knowledge/information

a) “lost” science. Some scientific discoveries are available only in languages other than English, right? That’s what they call it “lost” science, as long as it’s not translated into English (the lingua franca of science);

b) “hidden” science. A lot of scientific discoveries aren’t available for free, but are rather locked away behind expensive paywalls;

2. Funding/Monetization

It’s not a secret that a lot of great minds/scientists suffer from lack of $ for their projects/efforts/job;

3. Publishing

It’s not a secret as well that it’s really hard for a lot of discoveries to be published in top scientific journals, partially because of inadequate peer review process.

4. Collaboration

Two heads are better than one.

(fell free to mention additional problems I’m not aware of in the comments section)

(source – Pixabay)

All the problems aren’t separated, but rather tightly interconnected with each other.

Now, let’s discuss the aforementioned problems and possible blockchain-based (and non-blockchain-based) solutions in detail.

1. Access to knowledge/information

a) “lost” science

Shouldn’t be confused with “lost in translation”, which refers to loss of information during translation process.

While it’s extremely important to preserve the diversity of languages

To have a second language is to have a second soul

[Charlemagne]

and

there’re more than 7,110 languages spoken across the world

[How many languages are there in the world? [1]]

that diversity increases the risk that important discoveries get “lost”, unless they’re published in English.

For example, as early as the 1930s, German scientists showed a significant causal link between smoking and lung cancer, and published their research—in German (Proctor, 1999). But their findings were largely ignored until the 1960s when British and US scientists rediscovered the link, which eventually triggered public health policies and programs to reduce smoking.

[Is there science beyond English? [2]]

Given the enormous amount of research articles produced per year (around 2 million), I believe it’s hard to expect that the global community of translators will ever be able to translate all that by hand [3]. AI/neural network-based solutions could be of a lot of help in this case (for more information on this stay turned for my upcoming posts).

Would be nice if that solution is blockchain-based one, so that we could reward translators for their work.

What’s more, all that activity could help us to preserve languages. And

we're losing about one language a week, and by some estimates, half of the world's languages will be gone in the next hundred years.

[Lera Boroditsky on Ted Talks [4]]

b) “hidden” science

Those guys who “hide” their scientific discoveries behind expensive paywalls are doing this not because they are evil/greedy in their core, but rather because they’re human beings and need access to goods/services provided by the current monetary system.

There’s a number of open access journals. To my knowledge, the largest 2 open access journals in the world currently are Frontiers and PLOS One.

Don’t know yet how they (publishers/researchers) make money with such journals. Will try to discuss it in the upcoming posts of this series.

And, of course, you probably know about Sci-Hub which

is a website that provides free access to millions of research papers and books, without regard to copyright, by bypassing publishers' paywalls in various ways

[Wikipedia]

While this helps to solve the 1st problem to some extent, this makes the 2nd problem ($) even worse, because researchers lose their potential rewards.

Will discuss 2nd and 3rd problems together, and then possible solutions.

2. Funding/Monetization

So, as it was mentioned above, services like Sci-Hub may be one of the reasons why researches lose potential income.

As far as I know, the majority of scientific researches are funded by governmental grants [5].

Is that for the betterment of society in general if it’s the government, who decides what discoveries should be done/what you will/should know in the future?

What is the basis of their decision making?

– They are interested in particle behaviour. If you're a scientist, “Why do people kill each other?”, get out of that goddamn field. I don't give a shit about, whether the planets move and oscillate on the orbit while the world is going to hell. – Let’s get our priority. – We have problems now!

[Charlie Veitch interviews Jacque Fresco in London (2012)]

3. Publishing

I mentioned that peer review process is quite inadequate (to my knowledge) because of bureaucratism, because reviewers and authors don’t get fair rewards (or any at all?) for their efforts, unless they set that paywall.

All that leads to quite strange things like

many valid studies get at first rejected and are bounced around from journal to journal until they finally do get published. It happens even to the best research. Take for example this article on graphene. It was rejected twice and took at least 1 year to get published. And then, in 2010, went on to win the Nobel Prize in physics.

[Open Science can save the planet | Kamila MARKRAM | TEDxBrussels]

The article mentioned in the quote is

“Electric Field Effect in Atomically Thin Carbon Films”

What’s more, to my knowledge, it’s usually scientific researches with positive results what gets published, while the ones with negative results might be considered as non-relevant. And single scientific observations and individual insights usually are ignored as well.

That’s where the blockchain comes in.

(source – Pixabay)

To my knowledge, Bitcoin was initially designed to solve the problems of financial system and give control over the monetary system to all people [8].

Just like that, probably, would be nice to put science in the hands of all people (including general citizens), so that it’s all people who decides what they need to know, what researches should be funded etc.

That’s where ScientificСoin project comes in.

Note that there’re some other projects dealing with funding of scientific researches, but I’ll talk mostly about ScientificСoin today.

In a nutshell, this project tries to leverage the blockchain technology to help with funding of scientific projects. It focuses mostly on the projects evaluation by combining human power (” wisdom of the crowd”) with machine power.

In combination with the opinions of tens of thousands of people, even if they aren't professionally knowledgeable in the question, this algorithm will be maximally effective. The so-called “ wisdom of the crowd” will help thousands of decentralized experts in assessment of commercial value of the scientific projects

[Welcome to Scientificcoin BETA platform [9]]

All parties are going to be rewarded with SNcoin.

Remarkably, the beta-version of our platform has been already launched. Today ScientificCoin platform has a collection of more than 100 promising projects in various fields of applied and basic science

[Welcome to Scientificcoin BETA platform [9]]

https://www.youtube.com/watch?v=7i2lky0AC4w

As for publishing, one of the blockchain-based projects, which tries to make the process and peer review more adequate, is EUREKA. The projects aims to reward all parties of publishing process with EUREKA token and create a scientific review and rating platform for scientific findings.

https://www.youtube.com/watch?v=ScU9ytVP5Wc

in an open science world it can change because single observations and individual insights are just as important as group studies and the traditional journal article. And open science is an opportunity to think again about how we disseminate our research outputs, and ScienceMatters is doing just that.

[ScienceMatters presents the Eureka Platform]

What’s great about the project is that it will take into account all findings (positive, negative, as well as single observations and individual insights).

What is not great is that, given the activity of EUREKA team on Telegram, seems like it’s not very active.

Anyway, there’re other projects (like Orvium) with the same goal – making peer review/publishing process transparent and decentralized.

I’ll talk about them in the next posts of this series.

Well, actually the idea of crowdfunding for scientific projects with the help of online platforms comes from such pioneering platforms in this field like Experiment and Crowd.Science. But they aren’t blockchain-based. And blockchain brings a lot of benefits into this field. The idea of crowdfunding for scientific projects itself goes back to 1858, when

Alfred Russel Wallace (recognized as the co-founder of the theory of evolution) funded his work by selling specimens he collected from his field work to fund his research, so the theory of evolution was discovered because of crowdfunding science…

[source]

Another project called Scienceroot was going to become a blockchain-based scientific ecosystem, and solve as the problem of funding, as the problem of publishing. But, unfortunately, seems quite inactive right now (its web-site us unreachable and its Telegram group is quite inactive). You can find some information about it here.

Another similar (but more active) project is DEIP – a platform governed by researches, which will be used to raise money for scientific projects.

And, finally,

4. Collaboration

As I mentioned earlier, two heads are better than one.

Different people have different skills, and this interdisciplinary collaboration on a global scale might bring fruitful results.

As far as I know, GitHub history is going back to 2008. To my understanding, we actually already have a platform for scientists to collaborate. But this platform deals mostly with CS (computer science) and serves at the same time as a great educational platform for programmers.

But what about “GitHub” for other branches of science (biology, physics, chemistry etc.)?

Turned out that there’re some already like Authorea

Authorea is the leading collaborative platform to read, write, and publish research.

[source]

https://www.youtube.com/watch?v=x-IFkJc0ofo

(A quick introduction to Authorea)

Would be great if we had one day a similar one, but blockchain-based.

Aside from all that, people all over the world speak in different languages.

And, according to linguistic relativity theory and of its main contributors – Lera Boroditsky, our languages reflect reality around us and shape the way we think (which means that different language speakers think/perceive the environment differently), and

the even worse news is that right now, almost everything we know about the human mind and human brain is based on studies of usually American English-speaking undergraduates at universities. That excludes almost all humans, right? So, what we know about the human mind is actually incredibly narrow and biased, and our science has to do better.

[How language shapes the way we think | Lera Boroditsky [4]]

-> …biased

And in order to overcome those biases, people need to group together to solve the problems.

Looking at the problem from the point of view of different language speakers might increase the chances for the problem to be solved.

I’ll talk about linguistic relativity in one of the next posts.

Aside from those 4 problems, I’d like to mention that in order to become a scientist, you need some educational resources.

And, as you probably know, there’re plenty already like edX and Coursera.

Heck, there’re even some blockchain-based sort of open universities like OS.University.

is the first decentralized Education 4.0 platform.

[source]

where you will be able to be paid for studying and teaching others. This platform will solve a lot of other problems of the current education system and deserves its own post.

https://www.youtube.com/watch?v=KR9j-EeTwfI

[Open Source University: EdTech Blockchain Platform Explainer]

To motivate children/students even more, there’re some tournaments for scientists like International Natural Sciences Tournament and even blockchain-based platforms like Matryx.

(source – Pixabay)

In this post I’d like to start discussion of the systems which could help us to prevent such destructive events like you can see in the video below.

https://www.youtube.com/watch?v=qi6dAPBvyYU

According to CTIF Center of Fire Statistics report on World Fire Statistics № 24 (2019) (which can be downloaded at https://www.ctif.org/world-fire-statistics (CTIF_Report24_ERG.pdf file)) fires represent serious problem for humanity.

CTIF develops comprehensive world fire statistics by publishing annual reports which offer data on fire issues from 80 different countries and 90 capital cities.

source

The number of human deaths over a period of 1993-2017 averages to over 42,000 per year (based on the data obtained from 27-57 countries, which collectively represents 0.9-3.8 billion inhabitants of the Earth).

And the number of fires over that period of time averages to over 3,7 millions per year [5].

I don’t want even imagine, how much animals were killed in all those fires.

(source – CTIF_Report24_ERG.pdf file mentioned above)

The table below shows the number of fire deaths, fire injuries, fires themselves and other parameters by country based on statistics data of 2017.

(source – CTIF_Report24_ERG.pdf file mentioned above)

You can see that for example in Russia there were 132, 844 fires, 7, 816 deaths and 7, 816 injuries caused by fires in 2017 [5].

According to information provided by one of the team members of Internet of Trees startup

Around 340 million hectares of forest suffer from a fire every year. That’s more than 10 percent of the world’s forests. If they are not controlled, they can spread twice as fast as a walking pedestrian.

source

Typical causes

* dry weather

* high temperatures

* thunder strikes

* the magnifying glass effect [6]

> (a piece of broken glass that focuses sunlight heat on a particular point of forest) (source)

* electrical fire

* human carelessness

If you wonder what the deadliest fires in history are, then here’s some data from Wiki.

(source)

And below you can see the image of Camp Fire

the deadliest and most destructive wildfire in California history

source)

(source); Public domain)

It covered an area of 153,336 acres (62,053 ha) (almost 240 sq. miles), and destroyed 18,804 structures, with most of the damage occurring within the first four hours.

source)

-–> “...within the first four hours.”

A fire starting after 10 o’clock at night, under 50-plus mph winds, under absolutely dry, dry fuel beds, every one of those fires had a fighting chance to get going long before our firefighters could even be able to get there. So they all grew into major fires very quickly.” — CAL Fire Chief, Ken Pimlott.

source

So, the problem is that people find out about fires too late.

That’s where Internet of Trees comes in. The idea is to allow people be proactive rather than reactive when it comes to fires.

Before discussing their early-warning solution I’d like to talk a little about IoT (Internet of Things).

For the uninitiated, Internet of things (IoT) refers to the connection of devices via Internet (Wi-Fi) which can exchange data between each other and people (who can control them).

For example, there’re smart refrigerators which can notify you about the state of the food and communicate with your smart dishwasher or microwave (For more information –> https://en.wikipedia.org/wiki/Smart_home_technology).

Heck, there’re even systems which allow you to be notified (via SMS) when your flower needs some water or monitor the state of the soil in your greenhouse.

And we have Environmental Sensor Networks (ESNs). This is kind of IoT-applications for environmental needs.

They provide us sort of ‘virtual’ connection with the environment via a system of sensors which collect the data needed.

Ultimately they send the data to a central server where they can be collected, processed and analyzed by people [1].

“Internet of Trees” is not only the name of the startup, but is also the name of the system of special sensors/modules (called Fire Rangers) which can help you to monitor in real-time (data is processed within milliseconds) temperature variations, smoke air humidity and detect fires.

The latter happens when Internet of Trees modules find unusual patterns of the microclimate in the forests.

Batteries of those modules can last out up to 3-5 years.

Roughly, one module is needed per every hectare monitored.

source

The data is transmitted to the server which processes the data and sends notifications (via SMS or email) to firefighters, rescue teams, rangers, managers etc.

(the image (which serves as the header image as well) source)

https://www.youtube.com/watch?v=jhHaCx1LHa8

This contest is an attempt to promote scientific knowledge among community in a fun and interesting way with the help of molecules.

Some people like to travel around the world and tell others stories about what happens outside of our organisms/cells in other countries.

And with “Identify the molecule” contest you can try to travel inside our own organism/cells and cells of the organisms around us.

For more information about this contest read “Identify the molecule” league. Prize: knowledge + 5/10 XRP + 200/400 TMN post.

Prizes/bonuses:

The prize here is

1. knowledge

facts, information, and skills acquired through experience or education; the theoretical or practical understanding of a subject

[Oxford Dictionary of English, 3rd Edition, Oxford University Press, 2010]

That understanding of our own organism and organisms around us is the real prize in the case of this contest. No matter what happens (whether or not you get 5 XRP), you can win (can acquire the knowledge by investigating different sources of information, remembering and using it to your advantage in the future).

2. 5 XRP

3. 200 TMN

Aside from XRP I’d like to add TMN tokens.

For the uninitiated, TMN is the token of TranslateMe project (it’s about combining blockchain technology (NEO in this case) with translation industry).

The reason I’m going to add this token for the prize pool of this contest is not only because I have them, but because this contest is quite scientific, and TranslateMe project might help to solve the “lost” science problem.

For more on this you can read my post regarding TranslateMe (TranslateMe (or Decentralization meets Translation industry). Part 2. The “missing puzzle piece” of scientific ecosystem. General overview) (and other posts of that series).

For more information on crypto-bonuses for this league, please refer to “Identify the molecule” league. Prize: knowledge + 5/10 XRP + 200/400 TMN post.

Consider these tokens as a bonus.

Images and text are the clues for you to guess a riddle (the name of the molecule in this case).

Note that

a) even though this contest is called “Identify the molecule”,

-> molecule (singular)

sometimes it’s not just a molecule which is responsible for a specific function, but rather a complex of molecules.

Example:

cytochrome c oxidase (Complex IV)

is a large transmembrane protein complex… It is the last enzyme in the respiratory electron transport chain of cells located in the membrane.

source

b) some molecules/complexes have different names. For example, other names for cytochrome c oxidase (example above) are

Complex IV (mitochondrial electron transport). Cytochrome a3. Cytochrome aa3. Cytochrome oxidase. Warburg's respiratory enzyme.

source

Any of those names would be a valid entry.

c) Some almost identical molecules are grouped into classes / groups / families.

Example:

Helicases are divided into 6 groups. RecD and Dda molecules belong to helicases group (Superfamily 1 (SF1)). In this case you would need to guess only the name of the group –> Helicase/ Helicases.

d) Some proteins can have different forms – isoforms.

Example:

There’re trypsin 1 and trypsin 2. In this case you would need to guess only the general name – trypsin.

Important

In order to get TMN, you’ll need to have NEO-wallet and provide me your public NEO-address.

If you don’t have it yet, don’t worry, I published a post on how/where to get it (O3 wallet).

Note that NEO-addresses provided by exchanges will not work in this case (+ it's safer NOT to keep your funds on exchanges). It's highly recommended to get O3 wallet.

If there’re no winners on any stage, the prize will be distributed equally among all users who provided any guesses for molecules.

Rules

This contest lasts for 6 days.

Given that I don't see a comments section on Coil, I set up a Telegram group for this league, so that you could leave your reply with the guess there.

Leave your guess (1 guess only) in the Telegram group.

Don’t edit your comment/reply and don’t provide any evidence that your answer is correct.

The first user with the right answer is the winner.

I’ll provide the answer in the Telegram group.

Some of the clues have already been provided in the post.

Additional clues will be given in 2 days (on Monday, January 27, 2020, 20:00 ± 2 minutes UTC) (I’ll update this post).

And the rest of the clues will be provided in 2 more days (on Wednesday, January 29, 2020, 20:00 ± 2 minutes UTC) (I’ll update this post).

The reason is that some people might need less information to make conclusions that the others.

Additional clues will be added at the end of the “Riddle” section before the “Rules” section with “Edited” label.

The winner will be announced in that group (+ I'll publish a detailed review of the riddle after a while) on Friday, January 31, 2020, 20:00 ± 5 minutes UTC, so it's recommended to check that group on the 6th day.

I'll ask to provide me there your XPR-address.

I’ll transfer the tokens (XRP + TMN) (if the winner provides me his/her NEO-address) to the winner on that day (January 31) and add the transaction ID in the Telegram group.

I’m planning to run this contest every week.

So, you should expect to see the 2nd week’s riddle for January on Saturday, February 1, 2019, 20:00 ± 2 minutes UTC.

The riddle goes below.

(Efficacy and attitude towards the podcasts)

(Image was taken from PodMiners whitepaper)

In the previous post of this series I presented a general overview of PodMiners.

In a nutshell, PodMiners is about podcasting and broadcasting.

In this post I’d like to talk about educational potential of PodMiners.

Efficacy of podcasts

The problem of the efficacy of using audio and video podcasts for education has been dealt with in the investigations of a number of authors.

In the study conducted at the Manipal College of Dental Sciences, India, 80 first-year dental students were randomly divided into two equal groups (intervention group and control group). Both listened to live lecture. Then the first group worked solely with text books, while the second one with the text books accompanied by the podcast which presented only the highlights of the topics covered in the lecture.

The following flow chart illustrates the study design

[source]

In other words, after the lecture the first group received information through one sensory pathway, while the second group received it through visual and auditory pathways.

Then both groups underwent the test for assessment.

The study showed that the intervention group had a significant advantage in student performance over the control group [1].

As has been mentioned earlier, the students with better performance used two sensory pathways. It was shown (Scutter et al. and Boulos et al.) that information perceived through several sensory pathways is processed and stored more efficiently than that perceived through one pathway [[2],[3]].

(image was taken from Pixabay)

While some students prefer to use their study notes for revision, others prefer active listening for this purpose.

Scutter et al. have found that podcasts can help the latter group to grasp some additional information [3].

Similar findings regarding the efficacy of podcasts for educational purposes were observed in other studies.

The study conducted with African-American (AA) men living in the United States assessed the effectiveness of podcasts for educating inner-city AA men about diabetes prevention. Some potentially diabetic people might avoid developing this disease if they have appropriate knowledge, skills, and motivation. That’s where podcasts might help. The study showed that podcasts are helpful at educating inner-city AA men about diabetes prevention [4].

The idea of podcasts usage as a supplementary learning tool was supported in another study (Prakash SS et al.) [5].

However, one study (Vogt et al.), showed that there was no significant enhancement in performance of the students using podcasts [6].

No data can yet be available on the effect of podcasts on long-term retention and recall of the information. Additional studies should be done to elucidate the question.

Attitude of students towards the podcasts

The next point concerns the attitude of students towards the podcasts.

The study done with dental students showed that the majority of them found the podcasts useful because they could listen to the content repeatedly and at their own convenience.

On the other hand, some students found that the absence of images and diagrams in podcasts is a shortcoming [1].

Another study showed that audio/visual rich media recordings have positive impact on the educational experience. They helped students with their studies and reduced stress and anxiety [7].

The study assessing the usage of audio podcasts combined with tablet PC-enhanced learning for educational purposes in biochemistry showed that the students have a positive attitude towards it [8].

(or “Catch me (Cd2+) if you can”)

(One of the “heroes” of the 1st experiment – DUSP2 - with its catalytic domain (cartoon representation) with its conservative (V)-HC-XX-X-XX-R-(S/T) motif (highlighted with magenta). The image was created by me with the help of PyMol - open source tool for molecules visualization/exploration)

Introduction

You can find detailed definitions of specific bioinformatics/biochemical terms used in this post at the bottom of the post. Short cues will be given throughout the text.

Cadmium (Cd+2) is widely used in manufacture.

Cadmium harms kidneys, lungs, circulatory system, and influences bone tissue metabolism.

A lot of diseases are partially due to cadmium (including carcinogenesis).

So, it’s going to be quite interesting to try to analyze how exactly cadmium could affect some signalling pathways of the cell and what outcome of this impact could be (cell death/prolifiration…)). We are going to try to analyze MAPK (Mitogen-Activated Protein Kinases) signalling pathway.

Cadmium relationship with MAPK-signalling

To enter the cell Cd2+ as free ions or as a part of proteins/peptides uses transitory proteins: free Cd2+ can get into the cell through ion channels or with the help of carrier proteins, and Cd2+ complexes enter the cell with the help of receptor-mediated endocytosis. Cd2+ possesses “ionic mimicry”, i.e. it has similar properties to essential ions (which organisms need to stay alive). Similarly Cd2+ complexes demonstrate “molecular mimicry”, i.e. they ares similar to endogenous (originating from within an organism) biomolecules.

Once in the cell, Cd2+ can replace some proteins' ligands, which leads to Cd2+ accumulation in the cell [2, 3].

Cd2+ affects a lot of processes, happening in the cell: it inhibits DNA reparation, increases oxidative stress level in the cell, may lead to cell necrosis/apoptosis, affects MAPK-signalling and more [1].

Just imagine a big spider web for a second. This web probably consists of thousands of parts. Similarly, there’re thousands of biochemical pathways in the cell. When flies get into the web/trap, then the whole web react for that (so that a spider can “feel” that). Just like that, when something happens with 1 signalling pathway, then the whole network of metabolic pathways might react on that. World Wide Web could serve as an analogy in this case as well.

(The image above was taken from Pixabay)

In our case we will examine just 1 signalling pathway – MAPK-signalling pathway. What’s more, we are going to focus on just 1 “fragment” of this pathway – where DUSP phosphatases influence/regulate MAPK-signalling pathway.

(the image is from Wikipedia. Public domain. The parts of this image with better resolution is below. I placed this, so that you could get an overall picture of MAPK pathway. Mitogen-activated Protein Kinase Phosphatases (MKPs) are highlighted with the blue ovals.

When you hover over/click on MKP element on KEGG (see below) we get a set of DUSPs. That's how we get the DUSPs list you can see on the right top corner)

|| Useful tip

|| Almost the same image is on KEGG.

But that image is interactive –> you can click/hover over different elements to get the list of proteins and detailed information about each of them.

The KEGG PATHWAY database is a collection of manually drawn graphical diagrams, called KEGG pathway maps, representing molecular pathways for metabolism, genetic information processing, environmental information processing, cellular processes, organismal systems, human diseases, and drug development.

[KEGG]

Аt first glance (especially to the untrained eye) all this might look scary.

Pay attention to ERK, JNK and p38 kinases (highlighted with the green ovals). These are kinases regulated by DUSP.

In response to signals (mitogens, heat shock, osmotic stress etc.), coming from the outside of the cell (left part of the image with the overall process), a special group of enzymes activates and passes the signal to the nucleus (right part of that image). It’s is a multilevel process, in which kinases consecutively phosphorylate (add phosphate group) the next members of a cascade, which leads to their activation. This signalling includes MAPK kinase kinases (MKKK or MEKK), MAPK kinases (MKK or MEK) and MAPK themselves.

|| Think of relay race where athletes (kinases) carry a baton (phosphate group) and pass it to the next members (MAPK signalling). And think of phosphatases as the obstacles those athletes might face during that relay race (so that they might lose that baton (phosphate group)).

(image source – Unsplash; by Zach Lucero. Unsplash license)

As a result, a special group of genes activates. Activation of different groups of genes leads to different responses of the cell (proliferation (reproduction/division), cell death etc.).

|| This is to some extent similar to when your browser sends requests to Coil, and then you get different responses based on what URL was in the address bar of the browser.

Malfunctioning MAPK-signalling pathways are partially responsible for development of some diseases, including diabetes, rheumatic arthritis, neurodegenerative diseases and more [4].

As you can see, there’re 4 main MAPK-signalling pathways (in mammalian cells):

classical Ras/MAPK pathway,

р38-pathway,

pathway with c-jun N-terminal kinases (or JNKs) 1, 2, 3

and ERK5-pathway

The key property of MAPKs is the necessity of phosphorylation of both Thr and Tyr residues of a conserved Thr-X-Tyr (T-X-Y, where X is any amino acid) motif (within the activation loop) for those MAPKs to be activated [6].

(ERK (also known as MAPK1) ((surface representation)) (in complex with N-cyclohexyl-9H-purin-6-amine) as an example of MAPKs. T-X-Y is highlighted with magenta. 3D-structure (PDB-file) – 4QP1 in this case – was obtained from PDB. The image was created by me with the help of PyMol - open source tool for molecules visualization/exploration)

|| Useful tip

|| PDB (Protein Data Bank) is the central resource for 3-D structures of proteins/DNAs/RNAs

(The same as above, but cartoon representation)

MKPs

MAPK activity is regulated by a number of factors, including specific phosphatases (enzymes that remove phosphate group from a protein), including DUSP phosphatases. Dephosphorylation of any residue (Thr or Tyr) may lead to MAPKs inactivation [5].

Protein Phosphatases are divided into 5 groups, 1 of which is Class I classical cysteine-based protein phosphatases.

Dual-specificity phosphatases (DUSPs) belong to this group. In its turn, DUSPs are categorized into 6 groups, 2 of which are

Mitogen-activated Protein Kinase Phosphatases (MKPs) (also known as classical DUSPs) and atypical DUSPs.

The last 2 groups are known MAPKs dephosphorylation. However, for the sake of simplicity we are going to analyse only MKPs.

This group is involved in regulation of ERK, JNK and p38 kinases (which we mentioned above).

They are called dual-specificity phosphatases because they can catalyse tyrosine, as well as serine/threonine residues.

All they catalyse substrates in a similar way – catalytically active Cys residue of MKP reacts with phosphate group of the substrate, which is then gets removed (thus inactivating MAPK).

The key feature of this group is that its members have specific conserved catalytic motif – (V)-HC-XX-X-XX-R-(S/T), where X – any amino acid, “(...)” means that this residue is optional, V – Valine (symbol Val or V),

H – Histidine (symbol His or H).

They have N-terminal non-catalytic domains (which help to define cell localization of the enzyme and bind to the substrate) and C-terminal catalytic domain with the (V)-HC-XX-X-XX-R-(S/T), mentioned above, and some others [7, 11].

There’re 11 members of MKPs.

(The list was obtained with the help of HUGO)

|| HUGO

The resource for approved human gene nomenclature

[HUGO]

As for STYXL1 (the last MPK in the list), it was reported, that this enzyme is homologous to other MKPs, but is catalytically inactive (it has serine instead of cysteine in the catalytic site) [10]. Thus, we won’t analyse it.

MKPs family can be divided into 3 sub-families:

1. DUSP1 ⁄ MKP-1, DUSP2 (PAC1), DUSP4 ⁄ MKP-2 и DUSP5 –> nucleus;

2. DUSP6 ⁄ MKP-3, DUSP7 ⁄ MKP-X and DUSP9 ⁄ MKP-4 –> cytoplasm; ERK-specific;

3. DUSP8 (M3 ⁄ 6), DUSP10 ⁄ MKP-5 and DUSP16 ⁄ MKP-7 –> nucleus/cytoplasm; JNK ⁄ p38-specific;

[7].

Coil subscribers will get access to more details regarding MAPs, more images, short glossary and “References” section.

https://www.youtube.com/watch?v=4oyF7y87cW4

(header image source (Photo by Annie Spratt on Unsplash))