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Tuesday, 21 August 2018

Adaptive Evolution Study of MERS-Coronavirus lead to the identification of Spike Attachment mutations that enhanced entry in non-permissive cell line

Middle East Respiratory Syndrome (MERS) – Coronavirus (CoV) has its importance due to its known high mortality rate of about 35% as declared by World Health Organization (WHO). This virus is known to be originated from bats and passed then to humans through zoonotic spill over events. Previously several species that support MERS-CoV infection had been studied but until this paper published in Cell Reports shows the genetic mechanisms underlying cross-species adaptation.

Letko et. al. studied the adaptive evolution of MERS-CoV using broad taxonomic distribution of BAT species. (Source Cell Reports)
The research was lead by Vincent Munster who is a virologist at NIAID, NIH, USA and also Michael Letko, a visiting research fellow at Munster’s lab. Munster is primarily interested in evolutionary dynamics of viruses and also cross species transmission events, and in this current research published recently in August 2018 has shown the impressive study on hoast breadth and adaptability of MERS-CoV.

Letko selected 16 bat species with broad taxonomic distribution to screen in vitro MERS-CoV entry based on transfected DPP4 expression in non-permissive cell line. Among 16 species only one species Desmodus rotundus DPP4 (drDPP4) had shown least permissive to viral replication. Letko carry forward to understand the differences in MERS Spike that is involved in interaction with DPP4 receptor. Homo sapiens DPP4 and drDPP4 was found to have differences in two amino acid locations I295T and R317T respectively. Later when they try to express these mutations in non-permissive cell lines show that these mutations are important to restrict virus entry.

Letko hypothesized that MERS-CoV can adapt to these variation while serially passaging the virus, where try to look into the cytopathic effects of the virus. Serially passaging the virus leading adaptation of the MERS-CoV was observed where they identified two important mutations in Spike which allow the virus to entry into cell lines which was non-permissive for wild type MERS-CoV.
Later team wanted to understand the phenotype of these mutations, which show that the adaptive virus has developed alteration of surface charge of Spike that allowed entry of MERS-CoV.

The team conclude its importance of the study is focused on virus endpoint study where there perform wide selection of specie where assessing host breadth. Although team suggests that during viral adaptation there might be continuous accumulation of other mutations apart from virus spike which remained unclear in their study.

Journal Source:

Letko M, Miazgowicz K, McMinn R, Seifert S, Sola I, Enjuanes L et al. Adaptive Evolution of MERS-CoV to Species Variation in DPP4. Cell Reports. 2018;24(7):1730-1737.

Friday, 6 July 2018

Aspirin could be a new ray of hope to Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder, a type of dementia, that adversely affects memory, thinking, and behavior. It majorly affects elderly of 65 years and above, but there are chances of early onset of the disorder. There are approximately 9.9 million people suffering from the disease, with one new case every 3.2 seconds (source: The Global Voice on Dementia).

Alzheimer's disease is mainly caused by the accumulation of toxic beta-amyloid (plagues) due to its impaired clearance mechanism from the hippocampal region of the brain. Lysosomes are the major cellular degradative machinery that plays a pivotal role in cell homeostasis. Its abnormal functioning leads to a number of neurodegenerative disorders, Alzheimer's being of them.

Image source: Google Images
Aspirin has been known to enhance the lysosomal biogenesis in the brain cells by upregulating the transcription factor EB, which is the main regulator of lysosome synthesis. Researchers at the University Medical Centre, Chicago conducted various experiments on mice based on the above findings. They concluded that low-dose of aspirin administered orally can stimulate lysosomal biogenesis and thus, helping in clearance of stored toxic compounds in brain cells in Alzheimer's disease and other storage disorders.

Aspirin, also known as acetylsalicylic acid, is one of the widely used medications around the world for alleviating pain, fever, and inflammation. It is also an anticoagulant that works by inhibiting carboxylase enzyme and reduces both platelet aggregation and the following coagulation. Thus, also used in the long-term to prevent heart attacks, ischemic strokes, and blood clots.

Unleashing the new role of aspirin have helped in design new treatment regimen that could help in unraveling the mysteries of Alzheimer's disease.

For more interesting reads you can subscribe to my blog Scinergy21. Here is the link

Thursday, 26 April 2018

NEXTGENPCR: PCR in Under 2 Minutes

As written by Julia Travers; Canon BioMedical and Molecular Biology Systems have announced the upcoming release of the NEXTGENPCR thermocycler, which can carry out polymerase chain reaction within minutes. PCR is a lab technique used to create up to billions of copies of a specific segment of DNA. PCR, which is used in many branches of science and can typically can take hours, can now be completed in as little as two minutes. This thermocycler is described by the companies as representing the first significant advance in this process in 15 years. Dennis Snyder, senior director of global commercial operations for Canon BioMedical said: “Time to result is a constant concern for lab users, and we immediately saw an advantage in incorporating NEXTGENPCR as part of our portfolio. We are, therefore, delighted to secure this collaboration and look forward to rolling out NEXTGENPCR in the U.S. and Canada to both existing and new customers."

A press release explains that NEXTGENPCR achieves these speedy results by approaching the heating and cooling process in a new way; instead of heating and cooling Peltier blocks, it “moves standard format microplates rapidly across three temperature zones already set to the required denaturing, extension and annealing temperatures.” With this advancement in PCR technique, a three-step, 30-cycle protocol that amplifies a 100-base pair fragment can be carried out in less than two minutes. During PCR, temperature changes are implemented to separate strands of DNA, and then an enzyme is used to synthesize new strands that are complementary to the target sequence. Scientists amplify or copy target regions of DNA that they want to analyse or use in a new way. For example, the copies might be used to study gene functions or in forensics, medical diagnostics, ecology, molecular biology or molecular archaeology. PCR has been around since the 80s, when it was developed by Nobel Prize winner Kary Mullis. “MBS shares in our commitment to high-quality products that improve the laboratory experience,” Snyder said, adding that “offering the NEXTGENPCR products to our customers will shorten their protocols without requiring them to change their procedures." Gert de Vos, the inventor of the NEXTGENPCR, In addition to the plate, it was important to achieve high-speed PCR while also considering those things important to a user such as how much space the instrument takes on the bench, how much energy is used, and, in the end, how much the device will cost.

Image Credit: Canon BioMedical

NEXTGENPCR reportedly has an intuitive interface and can be easily integrated into existing lab protocols and routines. It also greatly reduces the power consumption levels of PCR.
NEXTGENPCR will initially be distributed in the U.S. and Canon BioMedical also holds distribution rights in Canada. Canon BioMedical is a wholly owned subsidiary of Canon U.S.A. and MBS is a Dutch biotechnology company. According to these companies, the global life sciences instrumentation market is predicted to reach a value of $85.1 billion by 2022, with the U.S. and Canada accounting for the largest share.


Wednesday, 7 March 2018

1.6 Billion Years Old breath discovered from India

1.6 million years of old bacteria was found from the pockmarks in rock found from central India. A research that published in the journal Geobiology identified most of the microbes are cyanobacteria. These ancient one of the oldest bacteria identified till now are capable to synthesize photosynthesis like modern plants using sunlight as energy and giving out oxygen as byproduct. This cyanobacteria are the earliest life forms paving away 2.4 billion of years ago started to supply oxygen to earth.

Fossilized bubbles formed by cyanobacteria on 1.6 billion years old fossilized mat obtained from Vindhyan Supergroup, central India. Credit: Stefan Bengtson. (Source PhysOrg)
Cyanobacterial excreted materials harden into several layers to form stromatolites. These stromatolites are found in very few places now. Therese Sallstedt, a biologist from Swedish Museum of Natural History with her colleagues has studied these rocks from Vindhyan Supergroup which might contain oldest fossils on earth.

In rock layers scientists found tiny spherical voids which was not ever found before. Researchers in their paper mentioned that in fossil microbial mats that thrive now are in hydrothermal water.

The bubbles are as small as 50 to 500microns which for comparison human hair is just 50micron in diameter. Some of the spheres were found to be squished which signify that they were once compressed before they formed rock. It is important to note that researchers also found filament structures which are probable remains of cyanobacteria.

The mats were once filled with oxygen as was produced by old cyanobacteria. The stromatolites contain higher concentration of calcium phosphate called phosphorites. Hence the discovery of oxygen bubbles within these phosphorites produced by cyanobacteria is a major discovery of early life.

Journal Source:

Sallstedt T, Bengtson S, Broman C, Crill P, Canfield D. Evidence of oxygenic phototrophy in ancient phosphatic stromatolites from the Paleoproterozoic Vindhyan and Aravalli Supergroups, India. Geobiology. 2018;16(2):139-159.

Tuesday, 6 March 2018

Video: How Bacteria Rule Over Your Body

The video here is adopted from the animation house of Kurzegat which is just as short as 8mins to explain how bacteria is associated with our health, feelings and even it allows us to crave for junk food.

Image: DiabetesDaily

Points to follow in the video:
1. Healthy microbiome is directly influence to our healthy immune system.
2. World of different microorganisms in our gut.
3. Know how microbiome can make us happy and sad.
4. Microbiome can influence our diet.
5. How to cure disease by fecal transplants.


Best Universities in Europe 2018 Rankings

Do you want to study in Europe? Then find out this year's best Universities of Europe as ranked by Times Higher Education.

Image Source: Times Higher Education

When we say Europe now its with and without UK.

Here are the top ten Universities ranked by Times Higher Education including UK:
1. University of Oxford, UK
2. University of Cambridge, UK
3. Imperial College London, UK
4. ETH, Zurich, Switzerland
5. University College London, UK
6. London School of Economics and Political Science, UK
7. University of Edinburgh, UK
8. LMU Munich, Germany
9. King's College London, UK
10. Ecole Polytechnique Federale de Lausanne, Switzerland
10. Karolinska Institute, Sweden

Here are the top ten Universities ranked by Times Higher Education excluding UK:
1. ETH Zurich, Germany
2. LMU Munich, Germany
3. Ecole Polytechnique Federale de Lausanne, Switzerland
4. Karolinska Institute, Sweden
5. Technical University of Munich, Germany
6. Heidelberg University, Germany
7. KU Leuven, Belgium
8. University of Amsterdam, Netherlands
9. Humboldt University of Berlin, Germany
10. Delft University of Technology, Netherlands.

Courtesy: Times Higher Education.

Thursday, 1 March 2018

How fruit juice affects the gut.

It was previously believed that fructose, which is the sugar found in fruit and fruit juice, is processed by the liver. However, a new study suggests that fructose is mainly processed in the small intestine. The study, which is published in the journal Cell Metabolism, reveals that processed high-sugar food and drink only spills over into the liver for processing when the small intestine becomes overwhelmed.
The recent findings add to the body of scientific knowledge on the effects of too much fructose on the body. We know from previous research that excessive consumption of sugar is harmful to the liver, and that chronic overconsumption causes obesity, increases resistance to insulin, and creates conditions for the onset of diabetes. Sometimes in the past, Medical News Today reported on a study that found that fructose-containing products such as sweetened drinks can increase the risk of non-alcoholic steatohepatitis, a form of non-alcoholic fatty liver disease, "which can lead to cirrhosis or liver cancer.”
The researchers, from Princeton University in New Jersey, used mice to study how fructose travels through the digestive system. Their findings suggest that there is a physiological difference in how the body processes different amounts of sugar. Rather than the liver processing all the sugar in the body, the team observed that more than 90 percent of fructose was processed in the small intestines of the mice in the study. The team found that fructose not absorbed into the small intestine is passed through to the colon, where it comes into contact with the microbiome, which is the microbiotic flora that inhabits the large intestine and colon.
The researchers explain that the microbiome is not designed to process sugar. So, while a person could eat a large amount of carbohydrates without exposing their microbiome to any sugar, this changes significantly when high-sugar products — such as soda and juice — are consumed. While the findings do not prove that fructose influences the microbiome, the team believes that "an effect is likely." They suggest that this link should be further investigated in future studies, as it may provide new insights into the adverse effects of high sugar intake.
In the study, the small intestine was found to clear fructose more efficiently after a meal. The team theorizes that during periods of fasting, such as in the morning or mid-afternoon, individuals may be more vulnerable to fructose as the small intestine has reduced ability to process it during these times. As study author Joshua D. Rabinowitz, of the Lewis-Sigler Institute for Integrative Genomics at Princeton University, explains, "We can offer some reassurance — at least from these animal studies — that fructose from moderate amounts of fruits will not reach the liver." "We saw that feeding of the mice prior to the sugar exposure enhanced the small intestine's ability to process fructose," Rabinowitz continues. "And that protected the liver and the microbiome from sugar exposure."
Rabinowitz says that the results support "the most old-fashioned advice in the world," which is to "limit sweets to moderate quantities after meals" and avoid sugary drinks outside of meal times.


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