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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.

The Sciences

Early detection crucial: Experts urge awareness as childhood cancer rates rise

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Dr Mampoi Jonas,Prof Jan Du Plessis

Childhood Cancer Awareness Month is gaining momentum as experts stress the importance of early detection in improving survival rates among young patients. Prof. Jan Du Plessis and Dr. Mampoi Jonas from the University of the Free State emphasize that recognizing the early signs of cancer can significantly enhance treatment effectiveness and increase survival chances.

Although childhood cancer accounts for just 1.2% of all cancers globally, its incidence is rising. In the United States, cancer is now the leading cause of death among children, and over 100,000 children worldwide succumb to the disease each year. The most common childhood cancers include leukaemia, lymphoma, brain tumours, nephroblastoma, and soft tissue sarcomas.

According to Prof. Du Plessis, early-stage cancers are more responsive to treatment and less likely to be fatal. However, due to the rarity of these cancers, misdiagnosis or late diagnosis is common, which reduces the chances of successful treatment.

“Cancer awareness is crucial for educating families, communities, and healthcare providers about the early warning signs,” says Prof. Du Plessis. “When people know what to look for, they are more likely to seek medical help early, improving the chances of successful treatment.”
Current research in South Africa is focused on standardizing treatment protocols and examining local factors affecting treatment outcomes. The South African paediatric oncology community is engaged in studies on Hodgkin’s lymphoma, neuroblastoma, retinoblastoma, and germ cell tumours. They are also investigating nutritional interventions to support patient care.

Key Early Warning Signs to Watch For: The Childhood Cancer Foundation South Africa (CHOC) outlines several symptoms that could indicate cancer:

• Seek Medical Help Early: For ongoing or worsening symptoms.
• White Spot in the Eye: New squint, sudden blindness, or bulging eyeball.
• Lump: In the stomach, pelvis, head, arms, legs, testicle, or glands.
• Unexplained Fever: Present for over two weeks, along with weight loss, fatigue, pale appearance, easy bruising, and bleeding.
• Aching Bones or Joints: Including easy fractures.
• Neurological Signs: Such as changes in walk, balance, speech, headaches, or an enlarged head.

Early detection is vital. If these symptoms are observed in a child or teen, it is crucial to consult a healthcare professional promptly. Raising awareness and educating the public about these early warning signs can save lives.

“Childhood cancer is a journey of resilience, strength, and hope,” notes Prof. Du Plessis. “It’s about more than just treatment; it’s about family, courage, and the simple joys in life.”

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The Sciences

Researchers using mushrooms to clean contaminated water

Mushrooms to the Rescue: UFS Researchers Pioneering Eco-Friendly Water Purification

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Prof Patricks Voua Otomo, Associate Professor and subject head of Department of Zoology and Entomology at the University of the Free State (UFS).

In an innovative approach to tackle South Africa’s escalating water contamination crisis, researchers at the University of the Free State (UFS) are turning to mushrooms for a natural and effective solution. Led by Prof. Patricks Voua Otomo, an Associate Professor in the Department of Zoology and Entomology, this noted research is exploring the potential of mycofiltration — the use of fungal mycelia for purifying polluted water.

South Africa faces a severe water treatment crisis, with a 2022 Green Drop Report revealing that fewer than 3% of the country’s 850 wastewater systems are compliant with required standards. This inadequacy exacerbates pollution in river systems, impacting both human health and environmental sustainability.

The United Nations’ Sustainable Development Goals (SDGs) underscore the urgency of addressing water quality. By 2030, billions are projected to still lack access to safe water, with targets aiming to enhance water quality and reduce pollution significantly.

Prof. Voua Otomo’s research focuses on the pollution drivers in the Qwaqwa region and explores solutions to mitigate their effects. His work highlights the local challenges posed by inadequate sewage sludge management and direct waste disposal into waterways, which has led to alarming levels of pharmaceuticals like anti-inflammatories, HIV medicines, and epilepsy drugs contaminating rivers.

To counteract this, Prof. Voua Otomo and his team are harnessing the power of fungi through mycofiltration. This method utilizes fungal mycelia to filter contaminants from water. The research, detailed in the UFS 2023 Impact Report, has shown promising results. For instance, a mycofilter using Pleurotus ostreatus (oyster mushrooms) successfully removed up to 94% of iron (III) and 31% of the pesticide imidacloprid from contaminated water.

“Mycofiltration works through adsorption, where contaminants adhere to the fungal surface,” explains Prof. Voua Otomo. The process involves using snails as bioindicators to assess improvements in water quality post-filtration.

The initiative, spearheaded by final-year PhD student Sanele Mnkandla, has potential beyond small-scale tests. The researchers are working on scaling up the technology to treat larger bodies of water, with varying filter sizes tailored to the volume and type of contaminants. Depending on the scale, filtration could take from minutes to days.

Mycofiltration of ferric iron aqueous solution.

Prof. Voua Otomo’s team is also investigating local applications, such as rainwater harvesting, to enhance the technology’s utility. The ongoing research, which includes technical notes and proof-of-concept studies, suggests that mycofiltration is a viable and cost-effective method for water remediation in South Africa.

This innovative approach offers hope for addressing the critical issue of water pollution, making mushrooms not just a food source but also a potential key player in safeguarding water resources.

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Society

Repurposed antidepressant shows promise as cost-effective treatment for breast cancer

The research, led by Dr. Asis Bala, reveals that Selegiline, a monoamine oxidase (MAO) inhibitor, could be repurposed as an anticancer therapeutic.

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Image by Waldryano from Pixabay

In a groundbreaking study, researchers at the Institute of Advanced Study in Science and Technology (IASST) in Guwahati, India, have discovered that Selegiline, an antidepressant drug, may offer a cost-effective alternative for breast cancer treatment. The research, led by Dr. Asis Bala, reveals that Selegiline, a monoamine oxidase (MAO) inhibitor, could be repurposed as an anticancer therapeutic.

The team’s findings, published in the journal Medical Oncology, demonstrate that Selegiline interacts with ten genes associated with various cancers. Their preliminary tests on six different cancer cell lines showed Selegiline’s efficacy in targeting both estrogen and progesterone-positive (ER+ & PR+) and triple-negative breast cancer (TNBC) cells. This research group has shown that Selegiline (L-deprenyl), an antidepressant drug from a class of drugs called monoamine oxidase (MAO) inhibitors, might be applied as anticancer therapeutics for breast cancer.

Unlike conventional therapies that rely on reactive oxygen species (ROS) to induce cell death, Selegiline operates through a different mechanism. It has been shown to inhibit protein kinase C phosphorylation, a process believed to be involved in its cancer-fighting effects.

Selegiline showed integrated networking with genes and diseases of different cancers. It also showed the inhibitory effect of PKC phosphorylation and ROS-independent apoptosis in breast cancer cells.

This novel application of Selegiline marks a significant step forward in cancer research. The study’s results highlight the need for further investigation into the drug’s in vivo efficacy, optimal dosing, and potential side effects. This approach could pave the way for more accessible and affordable breast cancer treatments in the future.

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