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Category: biotech/medical – Page 3

Beyond the crystal: Dynamic model captures loop flexibility in swine virus drug design

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to devastate the global swine industry, yet the structural basis of how small molecules block its entry into host cells remains unclear. Researchers at the University of Tsukuba and Mahidol University developed a refined model of the PRRSV receptor domain CD163-SRCR5 using state-of-the-art computational approaches, offering new avenues for rational drug design.

While traditional drug discovery often relies on static crystal structures, many biologically important proteins, including the scavenger receptor CD163-SRCR5, contain flexible loop regions poorly captured by crystallography. These loops are critical for recognizing and , making them challenging yet attractive drug targets.

In their new study published in The Journal of Physical Chemistry Letters, the researchers used (MD) simulations, ensemble docking, and fragment molecular orbital calculations to generate a dynamic, physiologically relevant structural model of the CD163-SRCR5 domain.

Muscle in Space Sheds Light on Ageing-Related Muscle Loss

Sarcopenia, which is a progressive and extensive decline in muscle mass and strength, is common with aging and estimated to affect up to 50% of people aged 80 and older. It can lead to disability and injuries from falls and is associated with a lower quality of life and an increased mortality. Apart from lifestyle changes, there is no current clinical treatment for sarcopenia.

Space flight with the associated absence of gravity and limited strain on muscles causes muscle weakness, a prominent feature of sarcopenia, within a short period of time, providing a time lapse view on age-related atrophy-associated changes in the muscle. This relatively short window of time in space provides a microgravity model for muscular aging and opens opportunities for studying sarcopenia, which normally takes decades to develop in patients on earth.

To understand the changes of muscle in microgravity, Siobhan Malany, Maddalena Parafati, and their team from the University of Florida, USA, engineered skeletal muscle microtissues from donor biopsies and launched them to the International Space Station (ISS) aboard SpaceX CRS-25. Their findings were published today in Stem Cell Reports. The microtissues were taken from both young, active donors and from aged, sedentary donors and cultured in an automated mini lab, which besides regular feeding and monitoring of cultures also enabled electrical stimulation to simulate exercise. On earth, the contraction strength of microtissues from young, active individuals was almost twice as much as the strength of tissues from older, sedentary individuals. After only two weeks in space, muscle strength trended to decline in the young tissues and was now more comparable to the strength of old tissues. A similar trend was seen for the muscle protein content, which was higher in young microtissues on earth compared to old microtissues but decreased in microgravity to levels measured in old tissues. Further, space flight changed gene expression, particularly in the younger microtissues and disturbed cellular processes related to normal muscle function. Interestingly, electrical stimulation could mitigate these changes in gene expression to some extent.

Two classes of FOXA1 mutations found to drive prostate cancer and therapy resistance

A new study from the University of Michigan Rogel Health Cancer Center, published in Science, sheds light on how two distinct classes of mutations in the FOXA1 gene—commonly altered in prostate cancer—drive tumor initiation formation and therapeutic resistance.

FOXA1, a key transcription factor that facilitates binding to DNA, is mutated in 10–40% of hormone-dependent prostate cancers. While common, the exact ways these mutations alter cancer cells have remained elusive—until now.

Rogel researchers, including Arul Chinnaiyan, M.D., Ph.D., S.P. Hicks Endowed Professor of Pathology and Urology, and Abhijit Parolia, Ph.D., Rogel Fellow and Assistant Professor of Pathology, used mouse models to understand the mechanisms underlying two major classes of FOXA1 mutations.

The ‘mind-bending’ bionic arm powered by AI

I was born without lower arms and legs, so I’ve been around prosthetics of all shapes and sizes for as long as I can remember.

I’ve actively avoided those designed for upper arms for most of my adult life, so have never used a bionic hand before.

But when I visited a company in California, which is seeking to take the technology to the next level, I was intrigued enough to try one out — and the results were, frankly, mind-bending.

Prosthetic limbs have come a long way since the early days when they were fashioned out of wood, tin and leather.

Modern-day replacement arms and legs are made of silicone and carbon fibre, and increasingly they are bionic, meaning they have various electronically controlled moving parts to make them more useful to the user. (Feb 2024)

BBC Click reporter Paul Carter tries out a high-tech prosthetic promising a ‘full range of human motion’

Continue reading “The ‘mind-bending’ bionic arm powered by AI” | >

Scientists Finally “See” Key Protein That Controls Inflammation

Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of Cincinnati’s Center for Advanced Structural Biology. This break

Autosomal Recessive Cerebellar Ataxia-27 Caused by a Novel Loss-of-Function Variant of Ganglioside-Induced Differentiation Associated Protein 2 in a Spanish Family

Question Are there more effective systemic treatment options for ERBB2-negative metastatic breast cancer and active brain metastases?

Findings In this nonrandomized clinical trial of 47 patients treated with utidelone plus bevacizumab, the central nervous system objective response rate was 42.6% according to the Response Evaluation Criteria in Solid Tumors version 1.1. The safety profile of this treatment approach was manageable.

Meaning These findings suggest that combination therapy with utidelone plus bevacizumab is a potentially viable treatment for patients with ERBB2-negative metastatic breast cancer and active brain metastases.

How a faulty transport protein in the brain can trigger severe epilepsy

Citrate is essential for the metabolism and development of neurons. A membrane transport protein called SLC13A5 plays a central role in this process and has previously been linked to a particularly severe form of epileptic encephalopathy.

Building on data from the recently completed RESOLUTE and REsolution flagship projects, scientists at CeMM have comprehensively studied the function and structure of the membrane transporter SLC13A5, experimentally investigating 38 mutant variants.

Their findings, published in Science Advances, shed new light on the mechanisms of this disease and lay the foundation for further research into epilepsy and other disorders.

How the brain links unrelated events: New insights into the amygdala’s role in decision-making

Our brain makes decisions based on direct associations between stimuli in our environment, but it often also does so based on events that initially appear unrelated. How does it achieve this? A recent study by the Cellular Mechanisms in Physiological and Pathological Behavior Research Group at the Hospital del Mar Research Institute, published in Proceedings of the National Academy of Sciences, offers new insights into this process and identifies the brain areas involved.

Using observations in , led primarily by first author and Ph.D. student José Antonio González Parra and supervised by Dr. Arnau Busquets, the research team was able to determine the mechanisms involved in how the brain makes decisions based on indirect associations between different . That is, instead of directly associating a specific stimulus with a rewarding or aversive situation, the brain establishes connections between two or more stimuli.

Dr. Busquets explains, “The project aims to understand how the brain enables us to make decisions based on indirect relationships between stimuli in our environment.”