Tiptoe through the thalamus…

This is how people looked at the brain in 1673. Things have changed.
Sketch by Thomas Bartholin, 1616-1680. 
Image via Wikimedia Commons. Public domain in USA.
In early October, the Allen Institute for Brain Science dropped a metric buttload of brain data into the public domain.
Founded by Microsoft co-founder Paul Allen, the Allen Institute for Brain Science is, not surprisingly, interested in, um, the brain. Specifically, according to the Institute’s web site, its mission is
“to accelerate the understanding of how the human brain works in health and disease. Using a big science approach, we generate useful public resources, drive technological and analytical advances, and discover fundamental brain properties through integration of experiments modeling and theory.”
Towards that end, researchers at the Allen Institute have been mapping gene expression patterns in the human and mouse brains, as well as neural connectivity in the mouse brain. Why? Well, because as a general rule, science requires a control. If scientists are ever to understand the brain – how we think, how we learn, how we remember things, and how all those processes get scrambled during disease or trauma – they first must understand what a typical baseline brain looks like. The Allen Institute is doing the heavy lifting of mapping out these datasets, one brain slice at a time.
In particular, they are mapping the gene expression and neural connectivity of every part of the brain, so that researchers can identify difference between regions, as well as the physical links that tie them together. Differences in gene expression patterns may reveal, for instance, that seemingly related regions actually have different functions, while connectivity, or brain “wiring,” could shed light on how the brain works. 
I’m a technology nut, so I’m less interested in the answers to these questions than in how we arrive at them. And thanks to the Allen Institute, I (and you) can view these data from the luxury of my very own laptop, no special equipment required. (To be clear, you can’t view the data from my laptop. You’d need my computer, and you can’t have it.) You don’t even need to be a brainiac (I couldn’t help myself) to do it.
Here’s how. Point your browser to http://www.brain-map.org/. From there, choose a dataset – say, “Mouse Connectivity.” This is a dataset of images created by injecting fluorescent tracer molecules into the brains of mice, waiting some period of time, then sacrificing the mice, cutting their brains into thin slices — picture an extremely advanced deli slicer — and taking pictures of each one to see where the tracer material went. The result is a massive collection of images, collected by injecting hundreds of mice, preparing thousands of brain slices, and represents gigabytes upon gigabytes of data, which Allen Institute researchers have then reconstructed into a kind of virtual 3D brain.
In the parlance of neuroscientists, this dataset represents a first-pass attempt at a “connectome” – a brain-wide map of neural connections. But it’s definitely not the last; the connectome is vast beyond reckoning. According to one estimate,
Each human brain contains an estimated 100 billion neurons connected through 100 thousand miles of axons and between a hundred trillion to one quadrillion synaptic connections (there are only an estimated 100–400 billion stars in the Milky Way galaxy).
Efforts are currently underway to map the connectome at a number of levels, from the relatively coarse resolution of diffusion MRI to the subcellular level of electron microscopy. That’s a story for another day, but if you’re interested in this topic, I highly recommend Sebastian Seung’s eminently readable 2012 book, Connectome: How the Brain’s Wiring Makes Us Who We Are.

Back to the Allen Institute datasets. When you click on ‘Mouse Connectivity’, the site presents you with an index of injection sites, 47 in all. Let’s click on “visual areas.” The next page that comes up is a list of datasets that include that region. For the sake of this example, let’s click on the first entry in that list, “Primary visual area,” experiment #100141219.

The resulting page contains 140 fluorescent images of brain tissue slices in shades of orange and green. Click one to see it enlarged. Orange areas are non-fluorescent – they didn’t take up the tracer, meaning they are not physically connected to the injection site. On the bottom of the window is a series of navigation tools – you can tiptoe through the thalamus if you’d like, simply by moving these sliders left-right, up-down, and front-back. Just like a real neuroscientist!
 

This is your brain (well, a mouse brain) on rAAV (a fluorescent tracer).
(Source)

You can also zoom in to the cellular level. Here’s a close-up of a densely fluorescent area of the mouse brain — you can actually see individual neurons in this view. 
 

This is a closeup of your brain on rAAV. (Again, if you were a mouse)
(Source)

Another option is to download the Allen Institute’s free Brain Explorer software, a standalone program that lets you view these data offline. With Brain Explorer you can “step” through the brain slice by slice, rotate it, highlight regions. It’s way cool, even if (like me) you don’t know very much about brain anatomy.
Here’s a screenshot from the application, showing gene expression data in the center of the brain.
 

Screenshot of the Allen Institute’s Brain Explorer software

If you’re interested in how the amazing researchers at the Allen Institute are doing this work, they lay it out for you in a nice series of white papers (here’s the one on the mouse connectivity mapping project). I recommend you take a look!
 
The opinions expressed in this post do not necessarily reflect or conflict with those of the DXS editorial team or contributors.

Biology Explainer: The big 4 building blocks of life–carbohydrates, fats, proteins, and nucleic acids

The short version
  • The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.
  • Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.
  • Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.
  • Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.                                                                                                      
  • The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.
The longer version
Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.

                                                  

Big Molecules with Small Building Blocks

The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.

We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.
Carbohydrates

You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.

When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.

Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.

The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.

Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.

On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.

The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!

If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.

The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?

If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.

In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.

Sugar and Fuel

A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.

Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.

Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.

Polysaccharides: Fuel and Form

Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.

Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.

Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.

Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.

The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.

Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.

The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.

That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.

These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.

Lipids: The Fatty Trifecta

Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.

Fats: the Good, the Bad, the Neutral

Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?

Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows.  Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.

Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.

Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.

Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.

The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.

You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.

In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.

A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.

Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.

Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.

Phospholipids: An Abundant Fat

You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.

Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.

There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.

Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.

The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.

Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.
As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.

Steroids: Here to Pump You Up?

Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.

But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.

Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.

Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.

Proteins

As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.

Levels of Structure

Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.

For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.

This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.

Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.

The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.

In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.

A Plethora of Purposes

What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.

As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.

Nucleic Acids

How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.

Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.

DNA vs. RNA: A Matter of Structure

DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.

So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.

RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.

DNA vs. RNA: Function Wars

An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.

These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.

RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.


 By Emily Willingham, DXS managing editor 
This material originally appeared in similar form in Emily Willingham’s Complete Idiot’s Guide to College Biology

On this Father’s Day, let’s remember the allofathers, too

A big brother, practicing the art of allofathering.

By Emily Willingham, DXS managing editor

On Mother’s Day, scientist and blogger Kate Clancy wrote an excellent post at Scientific American about allomothers, the people in your circle of friends and family who support mothers in their mothering. In thanking the allomothers in her life, Clancy included in that list her husband because men can be allomothers, too. Although this site is called Double X because we want to bring evidence-based science–and yes, some snark–to women, tomorrow is Father’s Day. So today, we’re shifting into XY gear and talking about allofathers. 

We all have or had fathers. Some for better, some for worse, some we may never have even seen. Many of us also have had other men in our lives who participated in a father role or who supported our fathers in the same way that Clancy writes about supporting mothers. The funny thing is, a Google search on “allofathers” confuses Google so badly that it actually declines to do that search and instead offers a search on “allomothers.” When you force it to search “allofather,” you get only three pages of scanty hits, some of which reference a more general “alloparenting.”

Why no love for the allofathers, Google? Fathers these days need allo support as much as mothers, or at least, the fathers I know do. As Paul Raeburn writes in this Father’s Day piece:

The grindingly slow recovery of the economy is making it hard for fathers to earn enough to help support their families. Those who do have jobs are working more hours, taking time away from checkers and family dinners. In many families, both parents are working, leaving less time for fathers and partners to work on their relationships with each other.

He notes that fathers these days thrive in a habitat that allows the time with family, time to do things other than make a living wage, although that remains an important feature of fatherhood and a key goal of every father I know. In fact, that emphasis means that my spouse–who is also the father of my children–is at work right now, on Saturday, after already putting in overtime through the week. Indeed, he may have to work tomorrow, on Father’s Day, and is looking at a midnight deadline Monday night. There will be no games of chess with Dad this weekend. 

The work is difficult enough and in a trying environment. And pushing against this need to work hard and keep a job is also a desire to have the kind of family time those of us in the United States have come to expect on weekends, particularly when we work salaried weekday jobs that ostensibly promise weekends off. That means that on top of the anxiety associated with stacking 20 or 30 extra hours onto a 40-hour work week to meet a tough deadline, my husband and my children’s father also feels angst about this inability to be a part of our family time. These are first-world problems, I realize, but that doesn’t make them any less real for us and our children.

So I’m allofathering for him. Yes, I’m the mother, but I’m also supporting my husband’s fathering role, in part by doing things that assure him that we’re all OK, and in part by doing things with our sons that people might think of as stereotypically “dad” activities: fishing, baseball, football, soccer, hiking. But I also have taken on the things he usually does around the house, like emptying the dishwasher Every Single Time, vacuuming, and doing the laundry. Bless the man, he usually does all the laundry. But I do miss the other allofathers in our lives.

We no longer live a stone’s throw or a short-ish drive from our extended family, but when we did and still when we visit, the allofathers are abundant. My children have uncles who take them fishing, monitor group infighting among nine cousins, catch snakes with them, play football and soccer with them, and take them on hikes and (fruitless) dove hunting. My husband does his share of allofathering for their children, reading books and playing with the youngest, making dinners, and serving as an ever-necessary playground monitor. And my children have a grandfather who builds things in his shop for them, closely monitors their BB gun target practice, wanders for hours with them in nearby woods to find animal bones, and patiently acknowledges every single mystifying LEGO construction and rambling imaginary story surrounding it.   

All of these alloparents expand the parenting and support and safety net for my children. They are the village raising my sons, and my children trust them implicitly. These allofathers summon up reserves of energy they probably didn’t know they had and in spending this time with their nephews or grandchildren, they add layers of complexity and different insights from father figures that my children wouldn’t otherwise have. They also model for children like my sons the many roles a man can have through life.

As humans, we fit several features of species that engage in this extra-parental parenting, including typically having a single offspring at a time, a relatively small number of offspring over a lifetime, and an extended period of parental investment, and being part of a highly social species with tight family bonds. It may be that as our culture evolves so that the father role expands into what was previously considered maternal territory, we need to more closely consider allofathers as well as allomothers. These factors that characterize us as an alloparenting species can add up to benefits and greater success for mothers and fathers and children alike. At any rate, I know that’s been the case in our family.

When I was growing up, I had four grandmothers and four grandfathers. Half of them were “step” grandparents, obviously, but I loved the fact that I had all of these grandparents, blissfully unaware in my childhood of the fractures and angst that had led to their presence in my life. Among these step-grandparents was the man who married my mother’s mother. They met over square-dancing, he a handsome architect, she a tiny, fiery single mother who could sew some kick-ass square-dancing outfits.

Through various unanticipated turns in Life’s do-se-do, after marrying my grandmother, this man one day became father to two of my cousins. From their early childhoods, he has been their father, even though for the rest of us cousins, he was our step-grandfather. Along with my grandmother, he committed himself to rearing them and being their parent, and today, in part thanks to his steady, calm presence, they are successful, happily married parents themselves. Without his stabilizing influence, their paths might have been much less straightforward. 

While what my step-grandfather did crossed over from alloparenting to being an actual father, my own children have a step-grandfather of their own who, I think, epitomizes allofathering. When we visit, he has a ready store of caps available for all the cap guns he buys them by the dozen (if you think there are a lot of guns in this post, there are; it’s Texas). He actually builds–builds–go carts and other motorized vehicles to take them buzzing around the large property where he and my mother live and maintains a fleet of bicycles for them to ride. He will drop anything to run a quick errand just because one of the youngest generation expresses a wish for a certain treat or toy. Ask him to make you an ax from a stick and a rock, and he’ll do it masterfully. He attends every volleyball, baseball, or basketball game my niece and nephew have and has simply been a steady and much-loved allofather figure in the lives of all of the youngest generation in our family.

When I think of men like these who enter into lives already structured around complex family interactions and who take on without comment or resentment the care and loving of the children in that family, I wonder if I could be as kind or selfless. Of course, I hope that I could. These little people are, after all, children, and they need love and support and classic grandparental spoiling and an understanding that parenting and parental love come in different forms and different ways of expression. To all the allofathers in my life, I–and my children–are extremely grateful. To all the fathers and allofathers out there, happy Father’s Day. And may I say, I think you all warrant more Google hits. 


***Special thanks to Kate Clancy for her post on allomothers and to Paul Raeburn for his post about the role of fathers today, which certainly drove my thinking about this topic.***

These views are the opinion of the author and do not necessarily either reflect or disagree with those of the DXS editorial team. 

Pregnancy 101: Fertilization is another way to come together during sex

Human ovum (egg). The zona pellucida is a thick clear girdle surrounded by
the cells of the corona radiata (radiant crown). Via Wikimedia Commons.
It was September of 2006. Due to certain events taking place on a certain evening after a certain bottle (or two) of wine, my body was transformed into a human incubator. While I will not describe the events leading up to that very moment, I will dissect the way in which we propagate our species through a magnificent process called fertilization.
During the fertilization play, there are two stars: the sperm cell and the egg cell. The sperm cell hails from a male and is the end product of a series of developmental stages occurring in the testes. The egg cell (or ovum), which is produced by a female, is the largest cell in the human body and becomes a fertilizable entity as a result of the ovulatory process. But to truly understand what is happening at the moment of fertilization, it is important to know more about the cells from which all human life is derived.
Act I: Of sperm and eggs

A sperm cell is described as having a “head” section and a “tail” section. The head, which is shaped like a flattened oval, contains most of the cellular components, including DNA. The head also contains an important structure called an acrosome, which is basically a sac containing enzymes that will help the sperm fuse with an egg (more about the acrosome below). The role of the tail portion of sperm is to act as a propeller, allowing these cells to “swim.” At the top of the tail, near where it meets the head, are a ton of tiny structures called mitochondria. These kidney-shaped components are the powerhouses of all cells, and they generate the energy required for the sperm tail to move the sperm toward its target: the egg.
The egg is a spherical cell containing the usual components, including DNA and mitochondria. However, it differs from other human cells thanks to the presence of a protective shell called the zona pellucida. The egg cell also contains millions of tiny sacs, termed cortical granules, that serve a similar function to the acrosome in sperm cells (more on the granules below).  


Act II: A sperm cell’s journey to the center of the universefemale reproductive system
Given the cyclical nature of the female menstrual cycle, the window for fertilization during each cycle is finite. However, the precise number of days per month a women is fertile remains unclear. On the low end, the window of opportunity lasts for an estimated two days, based on the survival time of the sperm and egg. On the high end, the World Health Organization estimates a fertility window of 10 days. Somewhere in the middle lies a study published in the New England Journal of Medicine, which suggests that six is the magic number of days.

Assuming the fertility window is open, getting pregnant depends on a sperm cell making it to where the egg is located. Achieving that goal is not an easy feat. To help overcome the odds, we have evolved a number of biological tactics. For instance, the volume of a typical male human ejaculate is about a half-teaspoon or more and is estimated to contain about 300 million sperm cells. To become fully active, sperm cells require modification. The acidic environment of the vagina helps with that modification, allowing sperm to gain what is called hyperactive motility, in which its whip-like tail motors it along toward the egg.

Once active, sperm cells begin their long journey through the female reproductive system. To help guide the way, the cells around the female egg emit a chemical substance that attracts sperm cells. The orientation toward these chemicals is called chemotaxis and helps the sperm cells swim in the right direction (after all, they don’t have eyes). Furthermore, sperm get a little extra boost by the contraction of the muscles lining the female reproductive tract, which aid in pushing the little guys along. But, despite all of these efforts, sperm cell death rates are quite high, and only about 200 sperm cells actually make it to the oviduct (also called the fallopian tube), where the egg awaits.

                                                

Act III: Egg marks the spot

With the target in sight, the sperm cells make a beeline for the egg. However, for successful fertilization, only a single sperm cell can fuse with the egg. If an egg fuses with more than one sperm, the outcome can be anything from a failure of fertilization to the development of an embryo and fetus, known as a partial hydatidiform mole, that has a complete extra set of chromosomes and will not survive. Luckily, the egg has ways to help ensure only one sperm fuses with it.

When it reaches the egg, the sperm cell attaches to the surface of the zona pellucida, a protective shell for the egg. For the sperm to fuse with the egg, it must first break through this shell. Enter the sperm cell’s acrosome, which acts as an enzymatic drill. This “drilling,” in combination with the propeller movement of the sperm’s tail, helps to create a hole so that the sperm cell can access the juicy bits of the egg.

This breach of the zona pellucida and fusion of the sperm and egg sets off a rapid cascade of events to block other sperm cells from penetrating the egg’s protective shell. The first response is a shift in the charge of the egg’s cell membrane from negative to positive. This change in charge creates a sort of electrical force field, repelling other sperm cells.



Though this response is lightning fast, it is a temporary measure. A more permanent solution involves the cortical granuleswithin the egg. These tiny sacs release their contents, causing the zona pellucida to harden like the setting of concrete. In effect, the egg–sperm fusion induces the egg to construct a virtually impenetrable wall. Left outside in the cold, the other, unsuccessful sperm cells die within 48 hours.  

Now that the sperm–egg fusion has gone down, the egg start the maturation required for embryo-fetal development. The fertilized egg, now called a zygote, begins its journey into the womb and immediately begins round after round of cell division, over a few weeks resulting in a multicellular organism with a heart, lungs, brain, blood, bones, muscles, and hair. It’s an amazing phenomenon that I’m honored to have experienced (although I didn’t know I was until several weeks later).

The Afterword: A note on genetics

 

A normal human cell that is not a sperm or an egg will contain 23 pairs of chromosomes, for a total of 46 chromosomes. Any deviation from this number of chromosomes will lead to developmental misfires that in most cases results in a non-viable embryo. However, in some instances, a deviation from 46 chromosomes allows for fetal development and birth. The most well-known example is Trisomy 21(having three copies of the 21st chromosome per cell instead of two), also called Down’s Syndrome.

The egg and sperm cells are unlike any other cell in our body. They’re special enough to have a special name, gametes, and they each contain one set of chromosomes, or 23 chromosomes. Because they have half the typical number per cell, when the egg and sperm cell fuse, the resulting zygote contains the typical chromosome number of 46. Now you know how we get half of our genes from our father (who made the sperm cell) and half from our mother (who made the egg cell). Did I just put in your head an image of your parents having sex? It’s the birds and the bees, folks—it applies to everyone!


All text and art except as otherwise noted: 
Jeanne Garbarino, Double X Science Editor
Twitter @JeanneGarb
Animations

I love this video, merely for the fact that it is of B-quality and has a sound track clearly inspired from a porn flick, not to mention that it helps to put things in a more visual context:

This one is great as it has more of a sci-fi Death Star appeal:




References and further reading:
  • Potter RG Jr. “Length of the Fertile Period,” Milbank Q (1961);39:132-162
  • World Health Organization. “A prospective multicentre trial of the ovulation method of natural family planning. III. Characteristics of the menstrual cycle and of the fertile phase,” Fertil Steril (1983);40:773-778
  • Allen J. Wilcox, et al. “Timing of Sexual Intercourse in Relation to Ovulation — Effects on the Probability of Conception, Survival of the Pregnancy, and Sex of the Baby,” New England Journal of Medicine, (1995); 333:1517-1521
  • Poland ML, Moghisse KS, Giblin PT, Ager JW,Olson JM. “Variation of semen measures within normal men,” Fertil Steril (1985);44:396-400
  • Alberts B, Johnson A, Lewis J, et al.Fertilization,” Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002.
  • How Human Reproduction Works” (contains a video of sperm fusing with egg)
  • Colorado State University’s “Structure of the gametes before fertilization” and “Fertilization.”

Survival is Gendered, According to Scholastic

[Editor's note: We were going to write this as a she said/he said sort of thing with Emily Willingham and Matthew Francis, but then Francis got all serious and did an analysis and stuff. So his smart analysis appears first, and Willingham's (not quite) equally sober chapter-by-chapter evaluation of the "girls" book follows.]

Last week Ryan North, purveyor of the excellent webcomic Dinosaur Comics, stumbled across a pair of books published by Scholastic. The books are titled For Boys Only: How to Survive Anything and For Girls Only: How to Survive Anything, which already should be a tip-off, but the tables of contents really hammer home a message. As North says, “Maybe – MAYBE – How To Pick Perfect Sunglasses is actually in the same class as Surviving When Your Parachute Fails.” However, it’s obvious that boys and girls are not expected to want to survive the same things, and that the very idea of survival is gendered in these books.

Thanks to the outcry, Scholastic has already announced they will discontinue the titles, which is great. However, I wonder why they approved them in the first place, and their announcement shows that they don’t really understand what the big deal is. My friend JeNel, who is a children’s librarian, points out that Scholastic’s displays are always gendered, with a lovely regressive social agenda. So, shall we break it down for Scholastic?

First, anytime you name two books “For Boys Only” and “For Girls Only”, put an alligator on the cover of one and a pink cell phone on the cover of the other, you’re telling your audience of impressionable children that these books aren’t going to be equivalent. It’s almost inevitable that the “boy” book is going to be full of adventure and the “girl” book is going to be full of social stuff, and that’s the case here. “Survival” for boys includes broken legs, tornadoes, and earthquakes (since boys are obviously the only ones who will ever experience those), while “survival” for girls includes frenemies, brothers, and teaching your cat how to sit. (I suppose treating cat scratches and bites is kind of a survival skill.) In other words, “survival” for girls is a set of potentially useful social skills – which I guess boys don’t need to know. I split the contents into five categories, and assigned each chapter to one of the categories. 

Here’s the breakdown:

  1. True survival skills, where the knowledge could save your life or at least help you cope with injuries (forest fires, flash floods, snakebites, etc.). Not all of these are likely to be experienced (such as polar bear attack), but at least they could happen. The score: “boys” 22, “girls” 0.
  2. Survival skills for science fiction or fantasy scenarios, which are fun, but will never happen in real life (ghost attack, vampire attack, dinosaur attack, etc.). The score: “boys”  4, “girls” 3.
  3. Useful skills and advice for daily life or unusual situations (dealing with annoying people, getting over rejection, etc.). Not all of these are of equal um…significance, unless you think picking the right sunglasses is equivalent to coping with bullies, but I didn’t want to break the categories up too much. The score: “boys” 0, “girls” 23.
  4. Skills and advice for sudden stardom or suddenly becoming rich, which are fun to dream about, I suppose. The score: “boys” 0, “girls” 3.
  5. Teaching your cat how to sit. The score: “boys” 0, “girls” 1.

Let’s ignore the hyperbolic titles, since obviously neither book is intended to actually teach you to survive everything. However, the implications are clear: Boys need to know how to survive broken legs and earthquakes, but girls evidently will never experience that sort of thing. (Or perhaps Scholastic is assuming the girls will always have a knowledgeable boy around to help out. That sentence caused me psychological pain to even type.) Similarly, boys won’t ever need help dealing with bullies, frenemies, or learning how to camp. Either that, or (as Greg Gbur suggests) girls already know how to deal with the hard survival stuff, so they don’t need the book.


———————————————————————–

So, like, talking on a cell phone held in
one hand while engaged in this activity is so
totally NOT a survival technique. 

GIRLS ONLY: How to Survive Anything!  
Table of Contents

  • How to survive a BFF Fight (Boys don’t have friends and fight with them? What is that thing they’re doing when they’re rolling around all over the floor trying to kill each other?)
  • How to Survive Soccer Tryouts (assuming very male David Beckham once had to do this)
  • How to Survive a Breakout (like this?)
  • How to Show You’re Sorry (because being a boy means never having to show you’re sorry)
  • How to Have the Best Sleepover Ever (My sons have sleepovers; just discreetly double-checked their gonads)
  • How to Take the Perfect School Photo (like this guy did?)
  • How to Survive Brothers (My sons have brothers, two each; they could really use some tips on this)
  • Scary Survival Dos and Don’ts (if it’s scary, don’t do it)
  • How to Handle Becoming Rich (Nooo! Not RICH!)
  • How to Keep Stuff Secret (It’s like, so hard, to like, keep your mouth shut, you know?)
  • How to Survive Tests (At first I thought this said “testes,” and I was confused. That said, apparently females do have more test anxiety than males. It’s because we’re too stressed about that perfect school photo).
  • How to Survive Shyness (Have you met my husband? No? That’s because he’s shy)
  • How to Handle Sudden Stardom (Boys and men never suddenly become stars. Ever)
  • More Stardom Survival Tips (because one chapter on stardom just isn’t enough)
  • How to Survive a Camping Trip (Boys never go camping. Or they automatically know how because they have testes. Or something like that)
  • How to Survive a Fashion Disaster (You see, fashion is an equal-opportunity threat, people)
  • How to Teach Your Cat to Sit (a critical skill, no doubt, but one boys need to know, too)
  • How to Turn a No Into a Yes (I just …  no)
  • Top Tips for Speechmaking (because we’ve never, ever seen a boy give a bad speech)
  • How to Survive Embarrassment (gentlemen, clearly no concern of yours, sudden erections during algebra notwithstanding)
  • How to Be a Mind Reader (I see what you’re thinking here. No. Just no)
  • How to Survive a Crush (So for boys, is the corollary “How to Survive a Lust?”, or what?)
  • Seaside Survival (More than half of the US population lives in a coastal county. I guess all the males in that portion are expendable)
  • How to Soothe Sunburn (like this fellow did)
  • How to Pick Perfect Sunglasses (living proof that boys could use some help with this, too)
  • Surviving a Zombie Attack (two of these people are male)
  • How to Spot a Frenemy (Paul, meet John. Mick, meet Keith. Simon, meet Garfunkel. Freud, meet Jung. See? Boys have frenemies, too!)
  • Brilliant Boredom Busters (Am copying these now for my three sons, for whom a houseful of toys, books, art supplies, games, videos, and movies simply isn’t enough)
  • How to Survive Truth or Dare (see “No., Just no” above)
  • How to Beat Bullies (Is this a recommended approach? ‘Cause I need to do some time traveling, if so)
  • How to be an Amazing Babysitter (You can start by not taking a gendered approach to every single facet of existence of the child you’re babysitting)

Vaccination attitudes are contagious

The power of social ties may be stronger than you think.

by Tara Haelle Continue reading