Trump's immigration ban

This post is a divergence from the usual science posts. As a scientist, immigrant, global citizen, I have been outraged by the President Trump's immigration executive order.

Here's his order:

I hereby suspend entry into the United States, as immigrants and nonimmigrants, of such persons (aliens from Iraq, Syria, Iran, Sudan, Libya, Somalia and Yemen) for 90 days from the date of this order. 

Other things in the order include the suspension of the Visa Interview Waiver Program, and the US Refugees Admissions Program.

Why are so many people outraged?
It was executed far too quickly. It was signed as an executive order, which means it did not go through the usual rounds of debates in Congress. Add to that, it took effect overnight, leaving people in mid-travels stranded. It is also way too broad, affecting both immigrants and non-immigrants, including people with valid visas and even green card holders. People are shocked. Enforcement has been chaotic. Perfectly documented law-abiding residents returning from vacations and business trips are now turned away at borders. This order is discriminatory, against what America stands for. People feel that it targets Muslim nations and can lead to a new wave of Islamophobia.

Let's just pretend for a minute that this is a legitimate way of reducing terrorism, this is still a terrible way of enforcement. Trapping hundreds and thousands of legal immigrants and residents outside their homes, away from their loved ones, with no warning, is a sure way to lose support.

What does this mean to you?
If you're a national of one of the 7 countries listed and currently residing in the United States, try your best to not leave the country. If you're currently travelling and are due to return to the US, there are immigration lawyers thinking of you and you may want to contact them. The American Civil Liberties Union has filed a lawsuit against this ban and has been awarded a nationwide temporary injunction to block deportation of people stranded in US airports by this ban. However this executive order has set the tone of how this administration is going to treat immigration issues. This "America first" policy can very well turn into an anti-foreigner policy. There is the worry that the temporary suspension may be extended or that more countries be added onto the list.

How does this affect science?
For years, scientists have been advocating open science, or free sharing science. From publications to be free for all to read, datasets to be free for all to access, to the scientific community to be open, free to share resources and enter collaborations. Many top institutions work on this model, with foreign scientists forming a significant part of the community. I was an international student in US universities for both undergraduate and graduate studies. In the lab group that I worked with, people with visas outnumbered citizens. Because the US is an academic powerhouse, it attracts the best people from everywhere. The diversity was integral to creating a vibrant atmosphere where bright minds from all over the world come together to create knowledge.

Conferences are an integral part of research. Many of the top conferences are held in the US. This immigration ban will affect entry of scientists. If prolonged, scientists are likely to put US conferences out of their agendas and go to Europe or Asia instead. The same goes for collaborations. This immigration move can easily isolate US from the rest of the world. Not so great for an "America first" policy.

Scientists have pushed back. Faculty members, Nobel laureates, Fields medalists and thousands of other scientists have signed a petition to stop this ridiculous immigration ban. Geneticist Michael Eisen has even decided to run for office, to have a more direct voice in policies.

In this recent nationalistic wave in the world, I urge all to look around you. Talk to immigrants, people who look different from you. Get to know them. You may be surprised to find that we are all human, we have very similar struggles, we are not so different after all. I look forward to the day when we can all live in harmony in a global community.

Craniofacial disease: Treacher Collins syndrome

A big question in Biology is how to get specificity from generality. Every cell has certain components that are essential for the life and function of the cell. For example, every cell has DNA which needs to be made into RNA and then to protein. Every cell has organelles like the nucleus and mitochondria. How do mutations in key components of every cell only cause disease in certain parts of the body?

One such example is Treacher Collins syndrome. Treacher Collins syndrome is a rare genetic disorders characterized by deformities in the facial structure. Typical features include downward slanting eyes, sunken cheekbones, small jaw, cleft palate and small or absent ears. Due to the physical deformities, many patients suffer from hearing loss, problems swallowing or breathing. Despite the many facial deformities, patients do not have mental retardation. In fact, a friend of mine who has Treacher Collins syndrome is working towards a PhD.

Since the symptoms of Treacher Collins syndrome are very specific and restricted to the face, you would expect the causal mutation to be in a face-specific gene. However, it is actually caused by mutations in TCOF1, POLR1C or POLR1D. These are genes involved in making ribosomal RNA. Ribosomal RNA are essential components of ribosomes. Ribosomes are molecular machines that are responsible for making all the proteins in the cell. Every cell has ribosomes and need ribosomes to survive. Hence as you can imagine, TCOF1, POLR1C and POLR1D are found in almost every cell in the body. Why then, do patients only show defects in the face when these genes are mutated?

A recent study has shed some light on how one of these genes TCOF1 can cause specificity. TCOF1 encodes a protein called Treacle. It has been known that Treacle works in the nucleoli, which are spots in the cell where ribosomes are made. Treacle has been shown to be involved in making ribosomal RNA as well as putting on modifications of the rRNA. When Treacle is broken, there are fewer functional ribosomes. One theory is that the cells which form the face are more sensitive to broken ribosomes and that is why patients have facial defects.

A large part of the face, including most of the bones and nerves, is formed by a type of cells called neural crest. The new study shows that when Treacle is not functional, cells that should become neural crest don't. Instead they become neurons. Why do they do that? Turns out that Treacle works with a complex of proteins to make proper ribosomes. The Treacle complex brings the RNA Pol I complex, ribosome maturation complex and rRNA modification complexes together. These complexes are responsible for making the RNA components of ribosomes, fold it in the right way, put on the right proteins and add the right modification marks.

The Treacle complex (red) needs to be ubiquitylated (Ub) to make normal ribosomes (green). Without Ub, ribosomes (blue) formed causes pluripotent stem cells to beoome neural progenitors instead of neural crest cells. As neural crest cells are involved in forming facial structures, this produces multiple facial defects in patients.

The Treacle complex itself needs to have a special mark, ubiquitylation, to be fully functional. Without ubiquitylation, or if the Treacle complex is otherwise broken, ribosomes can still form, but they behave differently from the usual ribosomes. Using a technique called ribosome profiling, the scientists looked at what proteins ribosomes are making. Normal ribosomes don't make proteins for specifying neural fate (brain, spinal cord) until neural crest specification (face) is finished. Ribosomes formed from a broken Treacle complex make neural precursor proteins earlier than usual. This turns stem cells into neurons earlier than they should. Because of this, stem cells don't get a chance to become neural crest. The lack of neural crest cells could explain why patients have facial defects.

This is the first explanation of how Treacle can cause neural crest/ face-specific defects. This is probably just one of the ways how Treacle mutations cause Treacher-Collins syndrome. Other ways will await further discovery.

For more information on Treacher-Collins syndrome and treatment options, please check out the following links:
FACES
Medicine Net

Sex determination

When we think about sex determination, we think about males and females. What controls whether you are a boy or a girl? Your genes of course. Males have a Y chromosome and females don't. Well not all animals determine sex the same way as we humans do. Here we are going to look at some of them and focus on some of the stranger ways of sex determination.

Why are there sexes?
Why do we have sexes in the first place? The short answer is that it increases genetic diversity and allows the species to better adapt to changing conditions.

Imagine there's a population of cats. Each cat has 2 copies of every gene. Let's pretend that a long-haired male cat meets a short-haired female cat and they decided to mate. When a cat makes a kitten, she only pass on half of her genes to the kitten. The other half comes from the father. They can't choose which half of their genes to pass. It's completely random. And so the kitten gets half of his genes from the mother and half from the father. Each kitten is different because it gets a different half of genes from each parent. So the kittens will have a variety of hair lengths, some have long hair and some short.

Say these kittens are suddenly shipped to Siberia where it is really cold. The ones with long hair are going to survive better than the ones with short hair and so at least some of the cats will do well. If for example, the short hair mother passed all her genes to her kittens instead of just half, then all the kittens are going to have short hair and perish in the cold Siberia winter. This is obviously a highly artificial example. No one ships cats to Siberia and leaves them out in the cold but you can see how increasing the variety in the population is beneficial to changes in the environment.

How do different animals determine sexes?
Most people are familiar with human sex determination using the X and Y chromosomes. The special sex chromosome, the Y chromosome, contains male-determining genes. Therefore people with XY are male and those with XX are female. This is true for all mammals.

Other animals do it quite differently. Birds for example also use a sex chromosome system. But for them, the females get the special chromosome. We call them Z and W to distinguish them from our system. Males are ZZ and females are ZW. The W chromosome carries female-specific genes.

Then there are animals that are even more different from us. Social insects like bees and ants don't have sex chromosomes. Instead, their sex determination depends on how many copy of every gene they have. As I mentioned before, we humans (and cats) have 2 sets of every gene, one from the father and one from the mother. Male ants have only 1 copy of every gene while females have 2 copies. All of the male ant's genes comes from his mother.

There are animals which don't use genes to determine sex at all. Reptiles like turtles and alligators determine sex based on the temperature at which the eggs develop. Sea turtles lay their eggs on the beach. The temperature at which the eggs are at in the middle third of the incubation determines whether the baby turtles will be male or female. At low temperatures, the embryo will develop into a male and at high temperatures, it becomes a female. The temperature threshold is only a few degrees apart and it could be the difference between being in the sun or shade.

Why are there different ways of sex determination? We don't really know but that's how evolution worked. There are advantages to using genes and ones for using temperature as the sex determination trigger. Systems using sex chromosomes are more stable. The sex ratio is always 50-50. Temperature dependent systems are more variable and sex ratios can change quite a bit based on the climate. This can be advantageous if for example, females and males mature at different rates. Eggs laid early in the season are of one sex while those later in the season are a different sex. This can make up for the difference in maturation time between the sexes.

Here's a really cool video that explains the above mentioned sex systems and more.

Animals that use both genes and environment to determine sex
Using sex chromosomes and using temperature seem very different. How did animals evolve such different systems? Was one of them the ancestral system and the other a younger system? How did the switch happen?

There are animals that use both genes and the environment to determine sex. One such animal is an Australian lizard with a really cool name, the bearded dragon (Pogona vitticeps). Like birds, its sex chromosomes are Z and W, where females have the special sex chromosome W. ZZ individuals are males but scientists recently discover females who are also ZZ. What's going on here?

Bearded dragon (Pogona vitticeps)
Image from Wikipedia Commons

Turns out that the dragons are also sensitive to the temperature at which the eggs are incubated. At low temperatures, all ZZ babies develop as males. But when the incubation temperature increases, some ZZ babies develop as females instead of males. The ZZ "sex-reversed" females are indistinguishable from the ZW females until you look at their chromosomes. The temperature effect is so strong that at the highest viable incubation temperature (37C), almost all the ZZs are females.

How does that work? Well, we are not sure. One model suggests that instead of thinking of a "female-determining factor" on the W chromosome, there is a "male-determining factor" on the Z chromosome. At normal, low temperatures, this factor is stable and ZZ babies are males. At higher temperatures, the male factor is degraded faster. With less of this male factor, the ZZ babies become female.

In the wild, there are ZW females and ZZ "sex-reversed" females. Both types of females are fertile and survive fine. But scientists have found that over the past 15 years, the ratio of ZZ females to ZW has been increasing. This may be due to climate change where the temperatures at which these animals live in increases. What will happen to the bearded dragon in the future as global temperature rises further is anyone's guess. Will the W chromosome be lost in the population? Will the ratio of males to females change? Is the bearded dragon more vulnerable or resilient than other animals in the face of climate change?

The bearded dragon is an example of a species that uses both temperature and genes to determine sex. It shows that the 2 sex-determining systems need not be mutually exclusive. Both have their advantages and disadvantages. They could have evolved independently and not one from another. As for whether there are other animals using both the environment and sex chromosomes for sex determination, we'll have to wait for scientists to find that out.

Feathered dinosaurs

If you wanted to know what a dinosaur looked like, the first place to look would be the Jurassic Park/ Jurassic World movies. They have made extinct dinosaurs real and even, to some extent, lovable. If Jurassic Park/ World theme parks were real and safe, it certainly looks like a very appealing place to visit. Dinosaurs are majestic creatures; the giant Brontosaurus, the vicious Tyrannosaurus, the nimble Velociraptor and others, have captured the imaginations of many. But were dinosaurs really like the ones shown in the movies? Were they covered in tough scales like crocodiles?

Since the early 2000s, a number of newly found dinosaur fossils showed something that shocked us all. These dinosaurs had feathers. How do scientists know that dinosaurs had feathers? Bones can be preserved for a long time, but soft tissue degrades rapidly. Dinosaurs lived 150-250 millions of years ago and that's a long time for tissue to degrade. Well, sometimes we get lucky, and find a very well-preserved fossil, usually preserved in stone. While the actual feathers are not present any more, traces of feathers can be seen engraved in stone. Feather shafts, which are the stiff middle vein of feathers, have a good chance of withstanding decomposition, and that's what we see in fossils today.

Here are a few examples of what feathered dinosaur fossils look like. These are 2 recently discovered dinosaurs. On the left is Zhenyuanlong suni. This was found in the Liaoning province in northeast China. This region has been a hotspot for finding feathered dinosaurs. Like most of the dinosaurs found in this region, Zhenyuanlong suni is not big. It is about 1.5m long, roughly the size of a large dog. However this is big compared to the other dinosaurs in the region, which are closer to the size of a cat.

Adapted by permission from Macmillan Publishers Ltd: Scientific Reports doi:10.1038/srep11775 and Nature (doi:10.1038/nature14423), copyright (2015)

This fossil is in a very good shape and all the limbs and tail are intact. What is interesting is that the imprints of the feathers are preserved. The brown regions around the skeleton (top left) show where feathers once lay, on the wings and tail. In the closeup of the arm (bottom left), you can take a better look at the spots where feathers were. Zhenyuanlong suni had arms which were completely covered with long feathers. Although still up for debate, Zhenyuanlong suni most probably was not able to fly.

On the bottom row lies Yi qi, another dinosaur found in China. This was unearthed in Hebei province, also in northeast China. Named for its wings, Yi qi literally translates into bizarre wings. Compared to Zhenyuanlong suni, elements in this fossil are harder to see so let me walk you through why its wings were deemed bizarre.

Once again you can see straight lines radiating from the bones (top right). They were Yi qi's  feathers. Feathers are found on the head, neck, arms and legs. Unlike birds (think chicken), many dinosaurs had extensive feathers on their legs, so that's not unusual.

What is really different about Yi qi is that in addition to feathers, it has a thin sheet-like layer around the hands (bottom right). In other words, its wings have both feathers and a webbed membrane over them. This is the first time a dinosaur has been found with the elements of both a bat wing and a bird wing. Think about a bat with feathers, or a bird with membranous wings. Pretty bizarre huh? The membrane is not as well preserved as the bones and feathers and scientists had a hard time getting the exact shape of the membrane right. Therefore, the extent to which the membrane helps Yi qi to fly or glide is still a mystery.

While we associate feathers with birds and flight, many feathered dinosaurs may not have been able to fly. What were the feathers used for then? Scientists have shown that dinosaur feathers are coloured. Like present day birds, these feathers may be used for camouflage, or like the peacock, for sexual display.

Next time you think of a dinosaur, imagine a colourful feathered beast instead of a dry scaly monster. It'll change your perspective about Jurassic Park.