Snapshot: How Do Scientific Articles Get Published?

The process of publishing a scientific article begins when a group of scientists set out to answer an outstanding question in their field. They then design and conduct a set of experiments to answer this question. Once the scientists feel that their results answer their questions, one of them – usually the one who did the largest number of experiments in the project – writes a first draft of their article.

Writing the Draft

This article draft is then read and edited by the other researchers who contributed to the experiments described in the paper. They will also be listed as its authors. Once all the article’s co-authors have agreed on a version of the article that they are satisfied with, they may choose to post it on a preprint server. This is an online forum where researchers can post scientific articles that have not yet been accepted for publication in a scientific journal. You can learn more about the differences between preprints and peer-reviewed articles in our past Snapshot on Preprints.

Getting Feedback: The Peer-Review Process

Whether or not the authors decide to post their article to a preprint server, they eventually send it to a scientific journal for publication. Different journals publish different types of articles, and the first thing that the journal’s editor will do is to check that it fits with what that journal usually publishes. This includes considerations like the field of science that the paper falls into, or the techniques used. If the editor accepts the paper, they then send it to a panel of scientists – usually two or three – who are experts in the article’s topic of research. These scientists – known as reviewers – read the paper and assess its quality. This includes asking questions like:

Did the authors do the right experiments to answer the questions that they were asking?

Were the experiments done correctly, or were mistakes made?

Do the results of the authors’ experiments mean what the authors claim that they mean?

The reviewers then send the editors a list of comments about the paper. These comments may include questions about the experiments, disagreements about what the experiments’ results mean, and requests for the authors to do new experiments to strengthen their conclusions.

If the reviewers think that it would take too much work to make the paper ready for publication in the journal, they will recommend that the editor reject the article. If this happens, the authors choose another journal to send their article to. That journal’s editor distributes the article to a new set of reviewers, and the review process begins again.

A notebook and pen lay next to a laptop with a fresh mug of coffee next to them.
What does it take to get a scientific paper published? There is a lot of writing and rewriting involved. Photo by Pixabay on Pexels.com

Revisions and Acceptance

If, on the other hand, the reviewers do not reject the article, the authors are given a set amount of time – usually several months – in which to respond to the reviewers’ comments. This could include doing new experiments, rewriting sections of the paper, and/or writing a response to the reviewers’ comments. The article may be sent between authors and the journal’s reviewers several times. However, once the reviewers all agree that their concerns about the paper have been addressed, the paper is deemed ready for publication. After additional formatting by copy editors, the paper is published in the next virtual and/or physical issue of the journal.

Between writing and rewriting a paper, having it read by multiple people, and doing new experiments, the process of publishing a scientific article can take months or even years! This is especially true if it ends up being sent to multiple journals. In the end, though, this process holds scientists accountable to their peers, allowing us all to be more confident in the findings of scientific research.

If you would like to learn more about scientific publisishing, take a look at this resource by the Understand Science.

Snapshot written by Amy Smith-Dijak  and edited by Celeste Suart.

Snapshot: What is Protein Degradation?

The Life Cycle of a Protein

No protein is made to last forever. Just as DNA and RNA direct a coordinated process for protein creation, there is also a process for proteins to be broken down by the cell. We call this proteolysis or protein degradation.

Proteins are broken down for a number of reasons. First and foremost, it’s a strategy for quality control. After a string of protein building blocks are put together, they are bent and folded into a  specific shape that allows the protein to interact with other proteins in a useful way. You can think of it like a daisy in a daisy chain- the stem needs to be carefully folded and tied or the daisy chain falls apart entirely. Cells have tools to identify misfolded proteins and break them down quickly to prevent problems.

Even beyond quality control, proteins have a certain lifespan within the cell. Regular protein recycling ensures that there is always an available supply of protein building blocks for the creation of new proteins. Removing older proteins also gives cells flexibility in terms of adjusting to environmental changes.

A bright blue plastic recycling bin.
Reuse and recycle. Protein degradation is how your cells break down old or broken proteins so their parts can be reused.
Continue reading “Snapshot: What is Protein Degradation?”

Snapshot: What is Statistical Significance?

What is statistical significance?

Anyone interested in research, be it experiments testing the effects of new medications or studies of human behaviour, is bound to eventually encounter the term statistical significance. Despite being a fundamental feature of research, the concept of statistical significance is often a source of confusion beyond the laboratories and classrooms in which it is frequently discussed. This confusion stems partially from the fact that the word “significant” has different meanings in and outside of research. In everyday language, the term significant typically refers to something important or considerable. Significance in research, or statistical significance, refers to the likelihood that a result can be explained by chance. The distinction between statistically significant and important should not be overlooked – a result that is not statistically significant may still be quite meaningful and have far-reaching implications!

 Research findings are always a matter of probability, not certainty. Researchers can never be entirely sure of a particular finding; they can only have some degree of confidence in it. Statistical significance relates to the amount of confidence that a researcher can have in a given result and whether this confidence is sufficient to accept the result as accurate.

person typing on a laptop
Not every research finding is real – many can be explained solely by chance. Statistical significance is a tool that allows researchers to identify results that are unlikely to occur by chance and, therefore, are likely meaningful. Photo by Ruthson Zimmerman on Unsplash

How do researchers evaluate statistical significance?

Researchers evaluate statistical significance through hypothesis testing, in which one tests data against a null hypothesis. For any experiment, the null hypothesis essentially states that there is no real difference between groups of interest. Accordingly, if the null hypothesis is true, any observed group differences can be attributed to chance. Hypothesis testing yields a test statistic called a p-value, which represents the probability of obtaining a result as or more extreme as that observed if the null hypothesis were true. The larger the p-value (from 0 to 1), the more likely the corresponding result occurred by chance.

Researchers often set their criterion for statistical significance at p<0.05, meaning that they will accept a result as significant if there is less than a 5% chance of obtaining it by chance. When a p-value is larger than the cut-off value for statistical significance, the data is considered to be consistent with the null hypothesis and unlikely to contain real relationships between variables of interest. Conversely, when a p-value is less than the cut-off value for significance, we can conclude that the finding is due to a real relationship between variables. In other words, we can reject the null hypothesis.

Why is statistical significance important?

Consider a researcher interested in whether a new drug improves motor control in adults with cerebellar ataxia. She runs an experiment in which half of the participants receives the new drug and the other half receives a placebo (which does nothing). She observes improved SARA scores in the participants who received the drug compared to those who received the placebo. This finding may indicate that the drug improves motor control. Alternatively, this finding may simply have occurred by chance, perhaps due to lucky sampling and group assignment. To determine whether the improvement in SARA scores is significant, the researcher must compare the p-value associated with the result to her criterion for significance. For example, if the p-value is 0.03 and the criterion for significance is p<0.05, the researcher can conclude with 95% certainty that the result is statistically significant, and there is a real relationship between the drug and improved SARA scores.

Probability graph visually showing the percentage likelihood of an event occurring due to random chance. Detailed description available in the image caption.
Graph illustrating the probability of possible results for a given experiment, with a criterion for statistical significance of p<0.05 and a result with a p value of 0.03. Based on a p value of 0.03, there is a 3% chance that a researcher would, by chance, obtain a result equal to or more extreme than the result observed (shaded green region). Figure made by Chloe Soutar.

A researcher can be more or less conservative in estimating statistical significance by applying different criteria. For instance, if we set the criterion for significance at p<0.01, we accept values as significant only if we would expect them to occur less than 1% of the time by chance. The criterion for statistical significance dictates how confident we can be in a given result. Understanding statistical significance thus allows us to make sound judgements about research findings and, in turn, how we invest our time, energy, and money.

To learn more about statistical significance, check out these articles and videos from Laerd Statistics and Khan Academy.

Snapshot written by Dr. Chloe Soutar and edited by Celeste Suart

Snapshot: What are Intrathecal Injections?

Drug delivery into the body can be achieved in several ways, from applying a medicated cream on the skin, to swallowing a pill, to injecting into a muscle or vein. Each route of delivery should at least achieve one thing – getting the drug to the part of the body where it can be helpful. Delivering therapeutic drugs into the brain, however, can be more difficult. Intrathecal injections are used to overcome this challenge.

Cartoon drawing of a woman's back, her hand resting on her lower back.
How do you get drugs to the brain? Through the back!

When a drug enters the body, it travels through the bloodstream until it reaches the target organs. But when a drug is destined to reach the brain, it needs to pass through a unique security feature known as the blood-brain barrier. The blood-brain barrier is important for keeping harmful and unknown substances out of the brain. It turns out that the majority of drugs injected into the body cannot pass this barrier. This poses a challenge for researchers and doctors for delivering important drug treatments to the brain.

One way that drugs can be delivered to the brain via the blood is by modifying their chemical nature slightly. This can help with entry through the blood-brain barrier. A more straightforward route of delivery is by injecting drugs into the brain space directly. Your brain inside your head and spinal cord along your back are bathed in and float in a liquid called cerebrospinal fluid (CSF).

CSF is a clear, colourless fluid that protects the brain from injury by absorbing shock, and it helps bring waste products out of the brain. Importantly, as CSF flows, it helps distribute substances around the brain. Injecting a drug directly in the CSF allows that drug to bypass the blood-brain barrier. One of the less invasive ways to access the CSF space is via injection through the thecal sac, the cushiony layer containing CSF that surrounds the spinal cord. This type of injection is therefore known as an “intrathecal injection”.

Intrathecal injections are injected into the cerebrospinal fluid around the spinal cord around the thacal sac (mid-back area). The injected drug then travels up the back to the brain.
A diagram of how intrathecal injections work. Image by Claudia Hung.

Intrathecal injections can be very helpful. They are used during surgeries to manage pain (spinal anaesthesia) and to deliver chemotherapeutic agents to target brain cancers. Intrathecal injections becoming an increasingly important route of administration for drugs investigated in neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, ALS, spinal muscular atrophy (SMA), and spinocerebellar ataxias (SCAs). These drugs include antisense oligonucleotides that can be delivered directly to the brain.

However, there are still a few challenges in giving medication through intrathecal injections:

  • Medication delivered by intrathecal injections may need to be given quite often. Since the CSF is replenished regularly, the substances are cleared quickly out of the brain and spinal cavity.
  • Intrathecal injections involve a needle being inserted into the spine. So they are more invasive and painful than a typical shot or swallowing a pill. This is especially true if multiple injections are needed.

Therefore, researchers and doctors are constantly trying to learn more about how drugs enter the brain. By studying this, they will make improvements in how medication is delivered to patients. Despite these challenges though, intrathecal injections are a clever and important way for delivering critical drugs to the brain to treat a wide range of diseases.

If you would like to learn more about intrathecal injections, take a look at these resources by the Allina Health and Cancer Research UK.

Snapshot written by Claudia Hung and edited by Judit M. Pérez Ortiz

Snapshot: What is the Blood-Brain Barrier?

What is the blood-brain barrier?

Blood circulates throughout the body in tubes called blood vessels, delivering oxygen and essential nutrients to different organs. However, not all things that circulate through the body can get into the brain. The blood vessels of the brain are slightly different. Their walls have a unique barrier that allows entry of some substances, but keeps others out of the brain. This unique security feature is known as the blood-brain barrier. This barrier allows passage of some substances, but can block out others. This is important because this provides access to substances that the brain needs to function, while keeping harmful substances at bay. The blood-brain barrier is therefore an important feature that keeps our brains and bodies healthy.

A crossing guard holds a stop sign with a brain on it in one hand. The other hand is held out to say "stop".
The blood-brain barrier is like a crossing guard. It helps some chemicals enter the brain, but it keeps others out.

How does the blood-brain barrier work?

The blood-brain barrier is the result of the coordinated effort of several players working together at a microscopic level. These players form physical and functional barriers to select what can enter or exit the brain. Like other blood vessels in the rest of the body, blood vessels in the brain are lined with a thin wall of cells called endothelial cells. Between these endothelial cells, there are gaps that can allow substances to exit the blood to the various organs in the body. However, in the brain, these cells form tight connections between the gaps to restrict large molecules from passing through.

Additionally, brain cells called astrocytes and pericytes wrap around endothelial cells to more strictly block what substances can get through. Very small molecules, such as hormones, can slip through this complex wall. Larger molecules, such as sugars, water, amino acids, and insulin, require help from proteins known as transporters to get through, and are a critical component of the blood-brain barrier.

What happens if the blood-brain barrier is not working properly?

Infections, abnormal inflammation, or prolonged stress in the body can contribute to larger gaps between the tight connections of the blood-brain barrier, seen in diseases such as multiple sclerosis or Alzheimer’s disease or with brain tumours. If the blood-brain barrier is not working properly, harmful substances that are usually kept out of the brain may enter and cause problems, and can start a harmful cycle of more infections and more inflammation.

What challenge does the blood-brain barrier post for brain therapies?

The blood-brain barrier is critical for regulating what enters or exits the brain to maintain a healthy brain. However, the blood-brain barrier also poses a challenge for researchers. Many potentially life-saving drugs developed for treating brain diseases and brain injury cannot pass through this barrier. To overcome this, scientists have devised novel ways to directly or indirectly deliver drugs into the brain. The therapeutic potential of smaller sized drugs (often called “small molecules”) is intentionally being tested as they can more easily pass from the blood to the brain.

Another alternative is making previously impenetrable drugs better at entering the blood-brain barrier. Scientists are trying to do this by attaching chemical modifications that “escort” them into the brain. Finally, direct access to the brain is created by injections that allow access to the brain space. We will talk more about this topic in our Snapshot on Intrathecal Injections next week!

If you would like to learn more about blood-brain barrier, take a look at these resources by the BrainFacts.org or The University of Queensland.

Snapshot written by Claudia Hung and edited by Judit M. Pérez Ortiz