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Feb, 2021

Mutation linked to Alzheimer’s may cause neuron blockages

Alzheimer’s is a disorder that is known to impact the brain cells progressively towards degeneration. The disease is also known as dementia or amnesia, wherein the person suffers from a progressive decline in memory or thinking abilities over time. The social and behavioral skills are disrupted and the individual faces difficulty functioning independently. To date, many pieces of research have been carried out to understand the reason behind the disease through a focused approach on amyloid aggregates. In Alzheimer’s, the amyloid peptides are known to aggregate leading to memory loss, it is considered to be the hallmark of the disease. Therefore, to find an effective treatment for Alzheimer’s, researchers are focused on these peptide aggregates. However, very little success has been achieved, where the scientist tried to inhibit the protein responsible for the production of amyloid- β (a protein called BACE1). Various failures have been observed by the researchers in the targeting of BACE1 in phase 3 clinical trials.

Recently, a team of researchers targeted another gene variant named GGA3, which is a potential risk factor for Alzheimer’s. The study has been published in Science Translational Medicine in November, highlighting the role of GGA in altering the BACE1 movement across brain cells. It is found that they cause aggregation of BACE1 protein leading to axonal damage as observed in the pre-symptomatic stages. Thus, it lays a path of hope for BACE inhibitors as an effective treatment for Alzheimer’s.

To date, researchers knew the cause of Alzheimer’s as the result of amyloid build-up. But questions like what precedes this build-up? What initiated the amyloid aggregation? What are the initiators of this pathogenic process and more such questions remain to be unknown. However, now the understanding of risk genes can be considered as an addition of a very important piece in the whole puzzle. The research may unravel the cause of neuro-dysfunction in much more detail than ever known.

“I think the core message from this paper is that this could be one additional primary pathogenic development that precedes amyloid plaques buildup,” -Henrik Zetterberg, Neuroscientist at the University of Gothenburg.

The present studies unfold certain genetic mutation in GGA3 gene that increases the risk of Alzheimer’s. The researchers found out that GGA3 protein plays a very important role in the transportation of BACE1 protein across the brain cells. Additionally, BACE1 is a protease that is considered to cleave the APP protein leading to the production of beta-amyloid and thus unwanted aggregation.

Some researchers consider that one of the biggest lacunae in understanding such complex problems is we often don’t merge the different sciences. The present study highlights how taking genetics, biochemistry, pathology, and cell biology together can pose the potential to unravel many difficult problems in science.

In the present research, the scientist learned that any mutation in the GGA gene or deletion of the gene segment can impact the transport of BACE1 protein across the axons. As a result, the protein aggregates in the axon region, leading them to swell. This is one of the reasons where this damage is being recognized among patients with Alzheimer’s. Early-onset of Alzheimer’s can be identified with the help of above mentioned axonal pathology.

“If a patient doesn’t have the GGA3 mutation, it’s still possible that defects in axonal pathology are caused by other genes. It is still valuable to know that once you have axonal pathology early, BACE accumulation could be a factor. So these mechanisms can apply more generally.”

The science of the BACE1 target has been used and reached till the phase 3 trials but failed. Because there were too many side effects observed that impacted the memory and thinking capability among people worse. It is stipulated that the blocking of BACE1 among Alzheimer patients is impacting the other crucial role played by BACE1 protein.

“The clinical trials that have been conducted, they had a pharmacological inhibition of BACE activity, up to ninety percent in some cases. So I think that what we learned is that probably we need to inhibit BACE to a lesser extent,” says Tesco, a researcher.

It is observed that the early damage to brain cells occurs about 20 years before the complete emergence of clinical symptoms. Thus, any treatment prepared to be given over a period of time can be considered as a good alternative. So, in the present case, if weaker inhibition of BACE1 opted for a long period the side effects will be reduced, and the chances of recovering increases.

Feb, 2021

Learning how SARS-CoV2 hijacks and damages lung cells

The emergence of the SARS-CoV2 virus has caused turmoil across the globe, forcing the researchers to study it in more detail. However, the behavior of the virus has been quite notorious. The frequent mutations and very less prior knowledge has caused some obstacles. However, scientists were acquainted that if they understand the underlying pathways in lung cells and host protein being impacted during the viral infection then there can be chances of identifying potential solutions. Considering this, scientists have recently found out how SARS-CoV2 hijacks and damages the lung cells.

The study was a multi-group collaboration between the Center for Network Systems Biology (CNSB), Center for Regenerative Medicine (CReM), and National Emerging Infectious Disease Laboratory (NEIDL). The researchers have mapped the molecular responses emerging from lung cells infected with the SAR-CoV2 virus. The finding of the study has been published in the Journal of Molecular Cell.

To understand the disease pathology and gain new insights to discover potential therapeutic targets, the researchers bioengineered the human alveolar cells. The cells when combined with high-end mass spectroscopy technology, it helped the researchers to identify potential host proteins and pathways changing during SARS-CoV2 infection. The researchers found out that lung cells infected with SAR-CoV2 have abnormal phosphorylation.

Phosphorylation is a very crucial protein modification process contributing to protein functionality in the cells. The proper phosphorylation process is important for healthy cells. However, it was noticed that the infection alters this process leading to cascading abnormal changes. These changes increase the chances of the virus to thrive within the cells and eventually destroy it.

The study also showed that as soon as the virus encounters the lung cells, it initiates exploiting the resources required for the normal functioning and growth of the cell. The invasion of the virus further disrupts the functioning of the cell and damaging it extensively. The resources used, powers the virus eventually leading to rapid proliferation and expansion in nearby regions. As a result, the exhausted and damaged cells undergo self-destruction and the virus starts infecting the cells in the vicinity while evading the body’s immune system. This cycle repeats continuously leading to the hijacking of lung cells and widespread damage.

The researchers examined lung alveolar cells from one to 24 hours after infection with SARS-CoV-2 to understand what changes occur in lung cells immediately (at one, three, and six hours after infection by SARS-CoV-2) and what changes occur later (at 24 hours after infection). These changes were then compared to uninfected cells. All proteins from infected and uninfected alveolar cells, corresponding to the different time-points were extracted and labeled with unique barcoding tags called “tandem mass tag.” These tags, which can be accurately detected only by a mass spectrometer, permit robust quantification of protein and phosphorylation abundance in cells.

“Our results showed that in comparison to normal/uninfected lung cells, SARS-CoV-2 infected lung cells showed dramatic changes in the abundance of thousands of proteins and phosphorylation events,” said Darrell Kotton, MD, BUSM, CReM.

“Moreover, our data also showed that the SARS-CoV-2 virus induces a significant number of these changes as early as one-hour post-infection and lays the foundation for a complete hijack of the host lung cells,” adds Elke Mehlberger, PhD, NEIDL.

Scientists also tried to examine the data obtained from the study to identify any potential opportunities for COVID-19 treatment. They found that about more than 18 existing drugs that have been already clinically approved can be re-purposed for the treatment. The research team believes that the current findings are very crucial and can contribute a lot to the field, specifically in terms of devising a cost-effective, robust and life-saving treatment to overcome COVID-19.

Feb, 2021

Five steps to write a paper: Beginners guide

Don’t you think writing a paper takes a lot of your time? It becomes more tedious if you are a beginner. That stands true because you might not know what to write and in which order. Well, we just want to tell you that you are not alone in this struggle. In this blog, we will be talking about some basic steps that can help you write a paper with great ease.

We have come across some of the clients who had told us about their struggles about writing the paper when told by the advisor. Writing a paper for a newbie means spending weeks on research, then writing and tweaking the work to get it in perfect shape. This may not still lead your work to the final stage, there still be alterations needed across multiple paragraphs, headings, conclusion, and more. The reality behind academicians facing issues in writing paper is that no one teaches them the right and easy way to do it. This often keeps most researchers in dark to figure out how to write a great paper that can be easily published in a high-impact journal.

Let us help you understand this process in detail. To start with, you need a well-defined process that allows you to write papers as per your need. Here are some basic five steps we think can be helpful to kick-start your paper writing experience.

Step 1: Defining the central message

When writing a paper, most people do the mistake of starting with an introduction without much clarity. This often leads to multiple edits at the end. To start, we suggest understanding what your paper wants to tell your audience. You must need to define a central idea/message around which the entire paper will be focused. For this, one must begin by visiting their research data. Pull out all data and inferences of your research. Find out what theory or argument you want to put forth. Create a rough storyboard with all the ideas, figures, and tables.

Step 2: Structuring your text

Once you know the central message, it is important to share it in a way where readers can easily understand. Many researchers do the mistake of haphazardly representing their ideas, which often reduces the interest of readers leading to low citations. This is where structuring the text comes into the picture, whenever thinking of writing a paper. You need to write your research content in an easy flowing manner. This helps readers to engage more and make the research content interesting and easy to comprehend. For this, you must plan your content in every section beforehand. Chart out how every section should start and end. We have seen many students starting every new section without raising an argument or question in the previous section. This is very important to maintain the flow of text, not only within a particular section but also across various sections. Thus, aligning the overall flow of the research paper.

Step 3: Catching the reader’s attention

The most important part of writing a paper is ‘Introduction’, as it decides the fate of your paper. Why so? Because the introduction is the first thing anyone will read and if you are not able to comprehend your central message of the paper here then your efforts may end in vain. For beginners, we suggest you, write the introduction at last. The introduction of a paper should be started in a way that catches the reader’s attention. You can start by highlighting the problem, stating some stats, taking events of history (relatable to the topic of research) at a glance, and more. An introduction is the section of your research paper where most of the storytelling happens. However, you have to make sure that the right facts and the central message is comprehended efficiently.

Step 4: Figures and the table

Do you know most of the people before actually reading the paper, just scroll through it to see the figures and table! This is why papers with good figures and tables get good citations. One of the important reasons for having figures and tables in your paper is that it adds a visual expect to it. The reader can comprehend the message briefly from the figures and tables. This often catches the interest of the reader at first glance, making them read the entire paper. So, focus on your figures and tables.

Step 5: Summary is the key

Well, most of the important parts of your paper are written. Now it’s time to summarise the entire idea with a take-away message. Writing a summary won’t take much of your efforts as you have already completed the tedious part. In this section, you must focus on your central message/argument and share the prospects of the research work. This is crucial because people will be keen on looking for further developments in your field of research.

These are the most basic five steps you can follow to kick start your research paper writing journey. However, if you still face any difficulty, feel free to connect with our team. We have a team of expert scientific writers helping academicians and corporates to get their finest work out in the high impact factor journal. We will be happy to assist you in writing a paper for you.