Many antibodies and hormones are produced rhythmically in our body. For example, melatonin is produced at night to help people sleep. The concentration of cortisol, a hormone produced in response to stress, peaks in the morning and decreases as the day goes on. These rhythmical changes can have many implications on clinical treatments. This April, Jyoti Madhusoodanan, a writer for The Scientist, spoke to various researchers on this issue.

Researchers at the University of Birmingham discovered that among people who received the seasonal influenza vaccination, those who received the treatment in the morning had higher anti-flu antibodies than those who received in the afternoon. This suggests that the varying levels of hormones and antibodies at different times of the day altered the effectiveness of the vaccine. The lead researcher of the study, Anna Phillips Whittaker, noted that if the timing factor was considered in clinical treatments, it would have a significant impact on health. “It’s such as simple, low-risk intervention that’s free to do, and could have massive implications for health,” said Whittaker.

Besides vaccinations, epidemiological data have shown that clinical treatments for illnesses such as arthritis, cancer, and allergies can be more effective if they are administered at certain times of the day. This idea of timed treatments is known as chronotherapy; it has existed for more than five decades, but has not been very popular among physicians. In recent years, research in molecular biology has further supported this concept. In a 2014 study done in the University of Pennsylvania, John Hogenesch and his colleagues discovered that 56 of the top 100 best-selling drugs in the U.S., such as esomeprazole, aripiprazole, and duloxetine, can cause periodic expressions in certain genes in mice. Hogenesch was positive about the future of chronotherapy because “now we have the groundwork to precisely understand a person’s clock and leverage that information for better health.” He claimed, “because of the molecular work, we’ve opened new doors here. This [idea] is not coming from left field anymore.”

Nevertheless, integrating chronotherapy into clinical treatments has a long way to go. Scientists who work on chronotherapy still face skepticism from the scientific community. In addition, putting chronotherapy into practice poses a lot of challenges because people’s circadian rhythms are different. Also, obtaining approval from the FDA to implement time-of-the-day indications for drugs has many obstacles. “Many of these observations are in the scientific literature but not on drug labels,” said Hogenesch. His team is currently trying to change this situation by investigating exactly how the time of the day affects the effectiveness of treatments, and by how much.

Reflecting back on the past research on chronotherapy, Stanford psychiatrist David Spiegel noted, “We’ve learned enough now to know that there are relatively easy-to-do, low-risk things that may have an effect on disease outcomes… I’d be surprised if there were any disease that didn’t have some circadian component.” To many chronobiologists, time is often neglected when doctors consider the right treatment and the right dosage for patients, and physicians should pay more attention to this important factor because “time offers another way to be precise,” said Hogenesch.

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Over the past forty years, DNA sequencing technologies have been advancing rapidly. It all started in the 1970s, when British biochemist Frederick Sanger first developed a technique to sequence DNA. This method used radioactive markers to indicate the type of each nucleotide. With the aid of polyacrylamide gel and X-ray, scientists were able to visualize the sequence of the nucleotides in DNA, giving them the very first look at this very important molecule.

This October, Catherine Offord a writer for The Scientist spoke to various researchers on the development of DNA sequencers.

“It was all very manual,” recalled Richard Wilson, at the McDonnell Genome Institute at Washington University in St. Louis. “We used to get the sequencing gels running, go have dinner and probably a few beers. Then we’d come back to the lab around two in the morning, take the gels down, put X-ray film on them, and develop them the next day.” Richard noted that after the gels were developed, his team would gather in the laboratory: some people would read the gel aloud, some people would type the sequence into a computer.

The Sanger method was widely adopted, and carried out manually around the world for a decade. Things were soon about to change. Sequencing instruments that were much faster and cheaper would soon be developed.

“It was clear to us that automating DNA sequencing was really going to be key to the future of biology,” said Leroy Hood, who co-founded Applied Biosystems Inc. (ABI) in 1981 to develop some of the sequencing machines that would drive this revolution. “Molecular biology was coming to the fore, and it was clearly central to understanding biological information in living organisms[…] Sequencing was going to become very, very important.”

“It was clear to us that automating DNA sequencing was really going to be key to the future of biology.”

ABI announced its first automated DNA sequencing instrument in 1986. Although it was based on the Sanger method, coloured, fluorescent labels were used to replace the radioactive labels. Instead of running the DNA through four different lanes, they ran them through only one lane because each nucleotide could be distinguished by its colour. A laser detector was used to determine the sequence, in place of the X-ray film. Though this technique was not cheap, costing between two to five dollars per sequenced nucleotide, sequencing became more practical and required less manual labour. Scientists not only were able to sequence a segment of DNA, but also the entire genome of a multicellular animal, such as Caenorhabditis elegans, a type of roundworm.

“We thought it would be transformative,” noted Kim Worely, a geneticist at Baylor College of Medicine, who was involved in the Human Genome Project. “Every lab around the world was spending lots of time analyzing one part of one gene. Giving people all the genes, all at once, so they could just do the biology would be a tremendous benefit.” As a result of the Human Genome Project, an international team of researchers were able to sequence the entire human genome by using this technique after spending ten years and three billion dollars.

The next wave of sequencing instruments that soon followed involved massive parallelization. Leroy Hood, described them as being able to produce “millions of different sequences simultaneously, but with very short reads.” The first commercially successful machines using parallelization was released by biotech company 454 Life Sciences in 2005. With a cost of less than one-sixth that of the conventional methods, these newly developed machines could sequence 25 million bases with 99 per cent accuracy in a four-hour run.

As a result of the Human Genome Project, an international team of researchers were able to sequence the entire human genome.

The following year, biotechology company Illumina bought Solexa, the most widely used sequencing machine today. Solexa was a cheap and effective sequencer for research and clinical labs. In 2014, Illumina released the HiSeq X Ten system, and reduced the cost of sequencing a human genome to less than a thousand dollars.
The latest research on DNA sequencing instruments focuses on using the motion of electrons to identify nucleotides. Researchers from the National Institute of Standards and Technology have proposed a design for the nanoscale electronic motion sensor, which can detect motions as tiny as those of an atom. This device is predicted to sequence at a speed of 70 million base pairs per second.

Leroy Hood, reflected back on the last thirty years of DNA sequencing, “Living through it, you were very impatient, and always wondered when we’d be able to move to the next stage (…) But in looking back, all of the things that have happened since ’85, they’re really pretty astounding.”

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Hydrogen is the most common element in the universe; at room temperature, it is a gaseous nonmetal. As a nonmetal, its electrons are unable to move freely. Eighty years ago, scientists first hypothesized that the metallic form of hydrogen might exist under high pressure and would have properties vastly different from its nonmetal form. Since metals have freely moving electrons, metallic hydrogen is predicted to be a superconductor.

One of the most notable examples of this phenomenon is at Jupiter’s core, which is believed to be made up of metallic hydrogen. Jupiter’s rapid rotation compounded with metallic hydrogen’s conducting properties might explain the planet’s magnetic field, which is about 20,000 times stronger than that of Earth.
The attempts to create metallic hydrogen have until now been fruitless because the pressure exerted on hydrogen was not great enough to transform it into its metallic form. In a press release, Gregoryanz stated, “the past 30 years of the high-pressure research saw numerous claims of the creation in the laboratory, but all these claims were later disproved.”

This January, upon creating metallic hydrogen, Gregoryanz and other researchers discovered that at pressure approximately 3.25 million times that of Earth’s atmosphere, hydrogen entered a new phase — phase V. This new form of hydrogen started to show properties similar to those of metals: their electrons became freely moving, and the molecules broke down to atoms. Their experiment further showed that the boundaries between phase IV and phase V seemed to be completely pressure-based, and independent of change in temperature.

However, the research team found that phase V wasn’t the fully metallic form of hydrogen, since there was evidence that some bonds between hydrogen might still be present. The physicists noted that their findings were “the onset of the predicted non-molecular and metallic state of hydrogen,” and higher pressure would be needed to achieve the purely atomic state.

In an interview, Gregoryanz explained that “[their] study presents the first experimental evidence that hydrogen could behave as predicted, although at much higher pressures than previously thought. The finding will help to advance the fundamental and planetary sciences.”

This breakthrough in the study of metallic hydrogen sheds new light on the structure of gaseous planets like Jupiter. It further suggests that metals and nonmetals are not immutable. A non-metal may transform into its metallic form under suitable conditions, and vice versa. Still, for a better understanding of metallic hydrogen, future experiments need to apply greater pressures to obtain the pure form of this elusive state of hydrogen.

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Set in contemporary Montreal, Backspring invites readers into the life of talented architect Eduardo Cabral. When Eduardo is on his way to meet his client at a local market, he is caught in a fire that destroys the site. He falls into a destructive spiral soon after. Consumed by self-doubt and anger, Eduardo becomes increasingly distant from his family and friends. The situation worsens after he is falsely accused of the arson; at work, Eduardo has to confront the rumours about his involvement in the fire. Meanwhile, his wife, Geneviève, who fruitlessly attempts to unearth the root of her husband’s aloofness, discovers her budding affections for Patrick, Eduardo’s best friend.

Narration alternates between the three protagonists and includes flashbacks showing the characters’ childhoods, giving readers a sense of immediacy. As a city where different cultures collide, Montreal mirrors the multiple identities of the characters.

Backspring was recently shortlisted for the 2016 Amazon.ca First Novel Award. In light of her nomination, the Daily spoke with McCormack through email about her novel.

McGill Daily (MD): Inter-cultural collisions are evident throughout the novel. Eduardo grows up in an immigrant family from Portugal. Geneviève’s mother is francophone, her father anglophone. She sometimes feels “too English to be entirely French, far too French to be entirely English.” What inspired you to focus on the issue of cultural hybridity and identification in Backspring?

Judith McCormack (JM): I have a mixed background myself (Russian Jewish on one side and Scots-Irish on the other), and so I’m fascinated with questions of hybridity, […] cultural fusions, and fissures. I grew up with a sense of being out of place, someone who didn’t fit the usual categories, with a “messy” identity that had to be explained. I also have a mild form of synesthesia (numbers appear in colours to me), so the book explores crossing boundaries and finding new amalgams – between cultures, between different spheres like architecture, science and law, and between people.

“But this is […] about a very human desire to understand and make sense of relationships between things.”

Of course, Eduardo is literally out of place, having emigrated from Portugal – this was partly inspired by the fact that I’ve lived in Little Portugal in Toronto for many years and have seen my neighbours wrestling with displacement, and their attempts to recreate aspects of their previous lives. Geneviève’s mixture of French and English also means a great dual of ambiguity for her, which is made more complicated by the historical tensions between French and English in Montreal, and indeed, within her own family – for example, her ne’er-do-well English father, and her French mother who functions within a bit of a cultural cocoon.

MD: The novel proposes a way to embrace one’s dual cultural identity, that is, to be the “whole” of each identity, instead of being the “half” of each identity. Geneviève envisions herself as being entirely French as well as entirely English. However, although a person with multiple cultural identities might feel that they do not completely identify as a member of any distinct group, this “in-between-ness” could also be an essential and unique part of their identity — how does the novel speak to this? Is striving to belong “entirely” to any cultural group necessarily desirable?

JM: Yes, I agree that “in-between-ness” can be embraced, but on a personal level, it’s easier said than done! Geneviève is genuinely trying to figure out why she experiences a mixed identity as half as good, rather than twice as good, not so much proposing a solution. But hybridity and ambiguity are also virtues in the book, for example […] Eduardo’s interest in the architect Gordon Matta-Clark who was exploring orphan spaces, and the spaces between spaces.

“I lived for two years in Montreal as a small child, and I think it must have crept into my blood in some indefinable way.”

As to how we navigate complex and fragmented cultural identities – h’mm. Write a book about it? I guess it might be different for everyone, but the main thing would be to value and delight in the subtlety and richness of these fusions. Or something like that.

MD: The novel weaves in many French and Portuguese words; for some, translations are offered whereas others are not. What purpose do they serve, especially for readers who are unfamiliar with these two languages?

JM: Well, most are translated, and I hope that the others are obvious from the context. But I also wanted to highlight the elegance and beauty of these languages in themselves, while at the same offering a taste of the outsider experience.

MD: Geneviève describes Montreal as “[a]n organism of its own. Complex, confounding, rich, bitter […] [It is a city of] its own glossary […] Francophone, Anglophone, allophone.” The passage about the Portuguese festival on St. Urbain is also memorable. Why did you choose Montreal as the setting of the story? What unique background does Montreal provide to the story that similar multicultural cities, such as Toronto, do not?

“I grew up with a sense of being out of place […], with a “messy” identity that had to be explained.”

JM: I lived for two years in Montreal as a small child, and I think it must have crept into my blood in some indefinable way. The history, the buildings, even the street names all seem to have a mysterious quality, and of course the combination of old and new diversities in this context is also remarkable. But this is a novel, so the sights, sounds and smells of the Portuguese festival are also there because their sensuality and colour just seemed to fit the story.

MD: Law attempts to prescribe precise definitions to things, while in real life, much ambiguity exists. How does your career in law give you a different perspective on cultural identification or a different approach to this issue?

JM: “Attempts” is certainly the operative word here – the astonishing variety found in real life can be very subversive of the kind of categorizing and sorting involved in law. In the book, my experience with law is reflected to some extent in our ceaseless (but often futile) attempts to organize, classify, and make sense of the chaos of life epitomized when Geneviève starts her tongue-in-cheek taxonomy of orgasms. But this is not so much about cultural identity as it is about a very human desire to understand and make sense of relationships between things.

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These birds’ unique way of attracting mates is performed at such a high speed that human eyes cannot see the astonishing phenomenon without advanced imaging tools. Soma, an associate professor at Hokkaido University, pointed out that even a normal digital video camera cannot capture their motion. By using a high-speed video camera with 300 frames per second, researchers were able to observe the tap dancing and determine that each step lasted about six frames, approximately 0.02 seconds. The tap dancing was at first assumed to produce vibrations and non-vocal sounds to attract other songbirds. As it turns out, although the tap dancing is invisible to unaided human eyes, the songbirds can see each other dancing because they have a much higher visual sensitivity. Sue Anne Zollinger, a researcher at the Max Planck Institute for Ornithology, referred to this heightened visual capacity in an interview with the Discovery Channel as a “higher flicker fusion threshold.”

Gahr and Soma observed this tap dancing behaviour in other closely related songbirds, such as the blue-capped cordon-bleu and the red-cheeked cordon-bleu, both of which are from the genus Uraeginthus. They inferred that three other species in the same genus – the blue-breasted cordon-bleu, the purple grenadier – and the common grenadier, may also tap dance in a similar fashion. Gahr noted in an interview with BBC, “maybe more birds are doing it, but it just has not been seen.”

Zollinger also explained in her interview that “the foot taps may also add to the acoustic part of the display, like a one-man band that sings while simultaneously playing the drums.” Gahr and Soma also noticed that while the songbirds were tap dancing and singing, they would also wave around a twig. Soma said it is predicted that “fine coordination or synchronization of dancing should relate to long-term pair bonding.” Soma also pointed out these socially monogamous birds are particularly selective when it comes to picking their mates; the songbirds only perform courtship displays to other birds they found attractive.

Additionally, this speedy footwork holds clues about the evolution of dancing in humans and other mammals. Dancing is a more intimate form of courtship for the potential mates, whereas singing is audible to any bird who can hear the sound, like an “advertisement,” as described by Soma. Zollinger has pointed out that the speed dancing not only serves as a visual component to the courtship display, it also suggests how physically fit the dancer is. “[Tap dancing is] quite complicated, to do all that without falling from the perch – it’s very acrobatic,” Gahr added.

Besides the unprecedented observation of tap dancing, the study documents the first known female songbirds whose courtship displays are as complex as their male counterparts’. Classical selection theory suggested that courtship displays evolved in males because females are believed to have the choice to select mates. However, in this study, dance performance varied amongst individual birds, but did not differ within sexes – both males and females escalated their dance when their mate was on the perch. This could suggest an angle for future studies in considering courtship as a two-way sexual communication, potentially focusing on how multimodal courtship display is evolved in both sexes to give us a more diverse and complex understanding of the bird kingdom.

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