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IIT Kanpur researchers visualize Duffy antigen receptor, advancing the fight against malaria and HIV

Researchers achieve landmark visualization of key Cell Receptor, paving way for new Drugs against infectious diseases. The new milestone can lead the way in combating drug-resistant infections and advancing the fight against diseases like malaria and HIV

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Professor Arun K. Shukla and his team. Image: By Special arrangement

A research team from the Indian Institute of Technology Kanpur (IITK), led by Prof. Arun K. Shukla from the Department of Biological Sciences and Bioengineering, has achieved a major scientific milestone by visualizing the complete structure of the Duffy antigen receptor for the first time. This receptor protein, located on the surface of red blood cells and other cells, serves as an entry point for harmful pathogens, including the malaria parasite Plasmodium vivax and the bacterium Staphylococcus aureus.

The groundbreaking research, published in peer-reviewed journal Cell, provides valuable new insights for scientists tackling antimicrobial drug resistance. With drug-resistant infections on the rise, this detailed visualization of the Duffy receptor structure could lead to significant advances in developing new therapies for drug-resistant malaria, Staphylococcus infections, and potentially other diseases like HIV.

“For years, researchers worldwide have been working to unravel the secrets of the Duffy antigen receptor due to its role as a ‘gateway’ that helps bacteria and parasites invade our cells and cause disease. Our achievement in finally visualizing this receptor at high resolution will enhance our understanding of how pathogens exploit it to infect cells,” said Prof. Arun K. Shukla from IIT Kanpur.

According to Prof. Arun K. Shukla, this knowledge will aid in the design of next-generation medicines, including new antibiotics and antimalarials, particularly as we face increasing antimicrobial resistance

According to him, this knowledge will aid in the design of next-generation medicines, including new antibiotics and antimalarials, particularly as we face increasing antimicrobial resistance.

“While the Duffy antigen receptor is common in most populations, a significant percentage of people of African descent lack this receptor on their red blood cells due to a genetic variation. As a result, they are naturally resistant to certain types of malaria parasites that rely on this specific ‘gateway’ to infect the cells. This highlights the crucial role of the Duffy antigen receptor in these diseases and suggests that targeting it could lead to new treatments,” added Prof. Shukla.

The research team utilised cutting-edge cryogenic electron microscopy (cryo-EM) to reveal the intricate architecture of the Duffy antigen receptor, illuminating its unique structural features and distinguishing it from similar receptors in the human body. This detailed insight is essential for designing highly targeted therapies that can effectively block infections while minimising unwanted side effects.

Prof. Manindra Agrawal, Director, IIT Kanpur said, “This remarkable achievement is a result of our institution’s support to cutting-edge research that addresses real-world problems and solidifies our standing on the global scientific stage. This will enhance our understanding of infectious diseases and help develop therapies for drug-resistant pathogen.”

The research team comprised Shirsha Saha, Jagannath Maharana, Saloni Sharma, Nashrah Zaidi, Annu Dalal, Sudha Mishra, Manisankar Ganguly, Divyanshu Tiwari, Ramanuj Banerjee, and Prof. Arun Kumar Shukla from IIT Kanpur. Additionally, researchers from CDRI Lucknow, Zurich in Switzerland, Suwon in the Republic of Korea, Tohoku in Japan, and Belfast in the United Kingdom also contributed to the study. This research was primarily funded by the Department of Biotechnology (DBT), the Department of Science and Technology (DST), the Science and Engineering Research Board (SERB), the DBT Wellcome Trust India Alliance, and IIT Kanpur.

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The timeless tortoise: Secrets to longevity and survival

The tortoise’s slow walk is not just a quirky trait — it’s a life philosophy, ingrained in their very survival

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Image credit: Pixabay

When we think of slow and steady, the image of a tortoise often comes to mind. But behind that unhurried gait lies a remarkable creature capable of defying time itself. The tortoise is among the longest-living animals on the planet. Their extraordinary lifespan has fascinated biologists and storytellers alike, leading us to wonder: how do these creatures live so long? Is it the giant tortoises of the Galápagos or the smaller, land-dwelling species that hold the key to longevity? Let’s take a deeper look.

A Life of Patience and Persistence

The tortoise’s slow walk is not just a quirky trait — it’s a life philosophy, ingrained in their very survival. These creatures are not in a race against time, they are its patient conquerors. Some species of tortoises can live well over a century, and in the case of the Giant Tortoise (known for its immense size), individuals have been documented living for more than 200 years. But why is it that these ancient reptiles live so long, while their cousins, the turtles, tend to have shorter lifespans?

In terms of lifespan, tortoises—especially the giant tortoises—lead the pack. A giant tortoise can outlive many other creatures, including their ocean-dwelling cousins, the turtles. While turtles generally live between 50 to 100 years, giant tortoises surpass this, sometimes even living beyond 150 years. In fact, Jonathan, a Seychelles giant tortoise living on Saint Helena Island in the South Atlantic, holds the record as the world’s oldest living land animal at 189 years old. Jonathan, who was born in 1832, has outlived all of his peers, continuing to thrive on the island where he was discovered.

The Science Behind Their Longevity

The secret to the tortoise’s longevity lies deep within its biology. While there are several factors that contribute to their long lives, two of the most significant are evolutionary adaptations and cellular processes that are finely tuned to conserve energy and maintain health over decades.

Image: Marzena P. from Pixabay

From an evolutionary perspective, tortoises face fewer natural threats in their environment compared to faster, more vulnerable animals. For many species of tortoises, survival has been less about outpacing predators and more about outlasting them. Many tortoises lay multiple eggs, often many more than a single clutch, and they continue to reproduce over several decades. This “quality over quantity” approach to reproduction ensures that their genes continue to thrive, while their individual lifespans stretch out.

Moreover, tortoises tend to have slower metabolic rates compared to other animals. Their bodies conserve energy by keeping their metabolic processes at a steady, slow pace. This “slow burn” strategy is key to their extended lifespans. A slow metabolism means that fewer cellular processes are damaged by the wear and tear of daily life, which translates into fewer health issues in old age.

One of the most fascinating aspects of tortoise longevity is the role of their telomeres. Telomeres are the protective caps at the ends of chromosomes that prevent them from fraying and tangling. Every time a cell divides, the telomeres shorten slightly. In most organisms, as the telomeres shorten, cells lose their ability to divide, eventually leading to aging. However, in tortoises, the telomeres wear down at an unusually slow rate, allowing their cells to divide without the usual detrimental effects seen in other animals. This slower rate of telomere shortening helps them avoid age-related diseases such as cancer and ensures that their cells remain healthier for longer.

Furthermore, some studies have revealed that tortoises are capable of a process called apoptosis—a form of programmed cell death—where damaged or dysfunctional cells are destroyed before they can cause harm. This controlled form of self-destruction in damaged cells helps prevent the formation of tumors and other age-related diseases, which is another reason for the tortoise’s impressive lifespan.

The Giants of the Tortoise World

When we talk about longevity in tortoises, we cannot overlook the giant tortoises of the Galápagos Islands and the Seychelles. These remarkable creatures have not only captured our imagination but have also become living symbols of resilience and endurance.

The Galápagos Giant Tortoise, for instance, can live over 150 years, and some individuals have even outlived the scientists who studied them. They were once thought to be heading for extinction, but thanks to conservation efforts, their populations have stabilized.

In India, a rare breed of tortoise known as the Aldabra Giant Tortoise has been known to live up to 255 years. This species, although not as well-known as the Galápagos counterparts, is another testament to the wonders of nature’s design.

Turtles, which are often found in aquatic environments, tend to live shorter lives, averaging about 30 to 50 years

But what about other, lesser-known giants? In Kasaragod, Kerala, India, a giant soft-shell turtle species was discovered in May 2021, which lives in freshwater, weighing over 100 kilograms! These giant creatures are living proof of the astonishing adaptability and longevity that nature has to offer.

The Mystery of Tortoises and Turtles

While all tortoises are technically land-dwelling creatures, there is an interesting distinction between tortoises and turtles. Turtles, which are often found in aquatic environments, tend to live shorter lives, averaging about 30 to 50 years. Tortoises, on the other hand, tend to have larger bodies, longer necks, and more robust shells. Their heavy, often plant-based diet plays a role in the additional years they add to their lifespan.

A surprising discovery made in the Seychelles in recent years has sent shockwaves through the scientific community: certain tortoises, once thought to be herbivorous, have been seen eating birds and other small animals. This has raised questions about the adaptability of tortoises in changing environments and has piqued the interest of researchers studying their survival strategies.

What Lies Ahead?

Despite all that we know about these extraordinary creatures, there is still much to discover. Researchers continue to study tortoises, particularly the giant species, to learn how their unique biological traits could benefit human medicine, particularly in the fight against aging and diseases like cancer. The discovery of their telomere dynamics, coupled with the ability to prevent cell damage through apoptosis, could one day revolutionize the way we approach longevity and healthcare.

For now, we can only marvel at the tortoise’s timeless existence, its slow, steady journey through the ages, and the lessons it teaches us about patience, resilience, and the secrets of life’s most enduring creatures.

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EDUNEWS & VIEWS

IIT Ropar unveils eco-friendly mechanical machine for knee rehabilitation

The introduction of this innovative mechanical CPM machine marks a significant step toward democratizing healthcare and improving rehabilitation outcomes globally.

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Representative image. Credit: Terry Shultz P.T./ Unsplash

In a major development for knee rehabilitation, researchers at Indian Institute of Technology (IIT) Ropar have introduced a revolutionary, low-cost solution to make Continuous Passive Motion (CPM) therapy more accessible to patients. The team’s newly patented innovation, the Completely Mechanical Passive Motion Machine for Knee Rehabilitation, is set to transform post-surgical recovery, especially in resource-limited areas.

Unlike traditional motorized CPM devices, which are expensive and reliant on electricity, the new machine operates entirely through mechanical means. Utilizing a piston and pulley system that stores air as the user pulls a handle, the device enables smooth, controlled knee motion to aid in rehabilitation. This design eliminates the need for electricity, batteries, or motors, making the machine lightweight, portable, and environmentally friendly.

The mechanical CPM machine addresses a key barrier to knee therapy: the high cost and power dependence of conventional electric machines. It offers a viable alternative for patients, particularly in rural and off-grid areas, where access to electricity is often unreliable. Its portability also enables patients to continue their therapy at home, reducing the need for frequent hospital visits or prolonged stays.

Knee rehabilitation is crucial for patients recovering from surgeries, as CPM therapy helps improve joint mobility, reduce stiffness, and speed up recovery. With this new device, IIT Ropar’s researchers are offering a cost-effective, sustainable option that could improve the lives of countless patients, especially in India, where advanced medical technology can be scarce in rural regions.

Lead researcher Dr. Abhishek Tiwari, along with his team members Suraj Bhan Mundotiya and Dr. Samir C. Roy, expressed optimism about the machine’s potential. “This device has the power to revolutionize knee rehabilitation, particularly in areas where access to sophisticated medical equipment is limited. It’s designed to be an affordable and eco-friendly solution that not only aids in recovery but also minimizes environmental impact,” said Dr. Tiwari.

The introduction of this innovative mechanical CPM machine marks a significant step toward democratizing healthcare and improving rehabilitation outcomes globally.

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Researchers develop AI algorithm to accurately detect heart murmurs in dogs

Researchers have developed AI Algorithm to detect heart murmurs in dogs, improving early diagnosis of cardiac disease

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Tutty, a Miniature Pinscher, is one of the popular small breeds known for its vibrant personality. Image credit: DD/EdPublica

Researchers at the University of Cambridge have developed a machine learning algorithm capable of accurately detecting heart murmurs in dogs—a critical indicator of cardiac disease, particularly prevalent in smaller breeds like the King Charles Spaniel. This innovative approach has the potential to transform veterinary care, offering an accessible tool for early diagnosis and treatment of heart conditions.

Heart murmurs are a key sign of mitral valve disease, the most common heart issue affecting adult dogs. Statistically, approximately one in every 30 dogs seen by a veterinarian presents with a heart murmur, with higher rates observed in small breeds and older dogs. Given the frequency of such conditions, timely detection is essential. Early intervention can significantly enhance a dog’s quality of life and longevity, making effective screening methods vital for veterinarians.

Dr. Andrew McDonald, the study’s first author from the Department of Engineering at Cambridge, emphasized the importance of early detection, according to a statement issued by the University: “Heart disease in humans is a huge health issue, but in dogs it’s an even bigger problem. Most smaller dog breeds will have heart disease when they get older, but obviously dogs can’t communicate in the same way that humans can, so it’s up to primary care vets to detect heart disease early enough so it can be treated.”

The Algorithm’s Development

The research team began with an algorithm initially designed for human heart sound analysis. Recognizing the similarities between mammalian heart function, they adapted this technology to analyze audio recordings from digital stethoscopes used on dogs. The algorithm demonstrated an impressive sensitivity of 90% in detecting heart murmurs, a level of accuracy comparable to that of expert cardiologists.

Professor Anurag Agarwal, the lead researcher and an expert in acoustics and bioengineering, noted the absence of a dedicated database for canine heart sounds. “As far as we’re aware, there are no existing databases of heart sounds in dogs, which is why we started out with a database of heart sounds in humans,” he explained in a statement issued by the University of Cambridge. “Mammalian hearts are fairly similar, and when things go wrong, they tend to go wrong in similar ways.”

The team refined the algorithm to not only detect but also grade heart murmurs

To build a robust dataset, the researchers collected heart sound data from nearly 800 dogs undergoing routine examinations at four veterinary specialist centers across the UK. Each dog received a thorough physical examination and an echocardiogram performed by a cardiologist, who graded any detected murmurs and identified underlying cardiac issues. This effort resulted in the largest dataset of dog heart sounds ever compiled.

Expanding the Dataset for Better Outcomes

Co-author Professor Jose Novo Matos, a small animal cardiology specialist, highlighted the need for diverse data to improve the algorithm’s effectiveness: “Mitral valve disease mainly affects smaller dogs, but to test and improve our algorithm, we wanted to get data from dogs of all shapes, sizes, and ages. The more data we have to train it, the more useful our algorithm will be, both for vets and for dog owners.”

The team refined the algorithm to not only detect but also grade heart murmurs, distinguishing between mild and advanced disease requiring further intervention. This innovation aims to empower general veterinarians, reducing the need for expensive specialized scans and consultations with cardiologists.

Promising Results and Future Implications

The algorithm’s performance was encouraging: it aligned with cardiologists’ assessments in over half of the cases, and in 90% of instances, it was within one grading unit of the cardiologist’s evaluation. Dr. McDonald pointed out the practical implications of these findings: “The grade of heart murmur is a useful differentiator for determining next steps and treatments, and we’ve automated that process.”

Novo Matos remarked on the transformative potential of this technology, seeing it as a supportive tool rather than a job threat. “So many people talk about AI as a threat to jobs, but for me, I see it as a tool that will make me a better cardiologist,” he said. With the veterinary profession facing time constraints and a shortage of specialists, this algorithm could streamline the process of identifying dogs that need urgent care.

A Path Forward for Veterinary Medicine

The researchers’ ultimate goal is to equip veterinarians with the means to make informed decisions regarding treatment, enhancing the quality of life for their canine patients. “Knowing when to medicate is so important, in order to give dogs the best quality of life possible for as long as possible,” said Agarwal.

Supported by organisations such as the Kennel Club Charitable Trust and the Medical Research Council, this research marks a significant step forward in the use of machine learning for veterinary applications. As technology continues to evolve, it holds the promise of not only advancing animal health but also improving the human-animal bond through better care and understanding.

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