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Roblox creator ups the game with $6.2m gift to reshape brain disorders treatments

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Roblox founder and CEO David Baszucki and his wife have donated $6.2m to develop a new software platform that could revolutionise the study and treatment of brain disorders, such as dementia.

Neuroblox is a cutting-edge programme that will model brain circuits to treat a range of neurological disorders like dementia, epilepsy, ADD, schizophrenia, and bipolar disorder.

It’s developer, biomedical engineer and neuroscientist Professor Lilianne Mujica-Parody, says the platform will allow researchers to explore the complexities of brain-based disorders by providing a blueprint for individualised care.

Taking its inspiration from Roblox – the popular virtual environment and creation system that allows users to programme and play games designed by other contributors – it’s hoped the platform will open up a world of modelling possibilities for neuroscientists without training in technical computing.

A screen shot of the Neuroblox interface.

Professor Mujica-Parodi said: “Right now, there is a disconnect between the aims of clinical research and the computational tools we have to exploit that research. Neuroblox is doing something fundamentally different. It’s trying to bridge that gap.”

Mr Baszucki and his wife, the best-selling fiction writer Jan Ellison Baszucki, have been prompted to make the multi-million dollar philanthropic gift after their son Matt’s bipolar disorder was put into remission from following a high-fat, adequate-protein, low-carbohydrate ketogenic diet – an area Professor Mujica-Parodi has explored in a first-of-its-kind study looking at the role of ketosis on brain functioning.

The investment from the Baszucki family includes $3.2m to help push forward with the development of the Neuroblox platform, which its backers believe could not only revolutionise mental health but shake-up the world of clinical neuroscience.

The remaining $3m will be used to create the Baszucki Endowed Chair for Metabolic Neuroscience at the Stony Brook University in New York. Professor Mujica-Parodi will be the inaugural holder of this chair, which recognises an exceptional researcher in metabolic neuroscience.

The gifts will be enhanced by an additional $550,000 from Stony Brook’s Presidential Innovation and Excellence Fund, designed specifically to accelerate the university’s highest ambitions.

Brain disorders like bipolar, Alzheimer’s dementia, and schizophrenia impact millions of families who have long struggled to find answers, including Jan and David Baszucki.

It was the couple themselves who reached out to Professor Mujica-Parodi after learning about her study exploring the role of ketosis on brain functioning.

Jan Baszucki said: “Here was a neuroscientist unveiling the mechanism by which ketones work to stabilize brain networks. This explained why a ketogenic diet gave our son his mind and his life back. We had to wonder if building on this knowledge by investing in metabolic neuroscience could be the first step toward helping others suffering from mental illnesses.”

Fuelled by enthusiasm for the potential of this project, Professor Mujica-Parodi quickly assembled a team of the brightest minds in computing, neuroscience, biomedical engineering and beyond to bring the Neuroblox vision to life.

Professor Lilianne Mujica-Parodi

She quickly realised that the potential impact of the Neuroblox platform extended far beyond bipolar disorder, however.

No longer was she creating just one solution by taking a circuit-based approach to the problem, but developing an infrastructure that could be applied to brain-based disorders more widely – including dementia, which is currently estimated to affect more than 55 million people globally.

This figure is expected to double every 20 years, with more than 80 million anticipated to be living with the progressive brain disorder by 2030.

David Baszucki said: “Lily is building a software platform where neuroscience researchers worldwide can refine, test and share models to help us understand how the brain regulates energy – a critical driver of mental health. Our family believes Neuroblox’s impact on understanding and treating brain-based disorders, including mental illness, will be transformative.”

Currently there is no clear understanding of which interventions may help with the treatment of brain disorders, whether that be lifestyle changes such as therapeutic nutritional ketosis to supplements and medication, and in what combinations and for which patients.

But it is hoped by creating a way to test possibly thousands of hypothesis in parallel, options can be eliminated through computation rather than guesswork. In short, Neuroblox would create the opportunity to forecast how the brain would respond to various interventions and at what rate over a set timescale.

American author and sixth president of Stony Brook University, Maurie McInnis, said: “Lily’s innovative approach to one of our most pressing societal issues – our mental health and well-being – is inspiring. It underscores our commitment as an institution to advance knowledge that will have a long-term, significant impact on the world,;

“We could not be prouder of these efforts, and we are thrilled that the Baszuckis have chosen to invest in Lily’s trailblazing work in a way that will undoubtedly change lives.”

 

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Evening exercise benefits elderly hypertensives

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Evening exercise benefits elderly hypertensives

A study conducted at the University of São Paulo with 23 volunteers found that aerobic exercise performed in the evening benefits elderly hypertensives more than morning exercise.

Aerobic training is known to regulate blood pressure more effectively when practiced in the evening than in the morning.

Researchers who conducted a study of elderly patients at the University of São Paulo’s School of Physical Education and Sports (EEFE-USP) in Brazil concluded that evening exercise is better for blood pressure regulation thanks to improved cardiovascular control by the autonomic nervous system via a mechanism known as baroreflex sensitivity.

Leandro Campos de Brito, first author of the article, commented: “There are multiple mechanisms to regulate blood pressure, and although morning training was beneficial, only evening training improved short-term control of blood pressure by enhancing baroreflex sensitivity.

“This is important because baroreflex control has a positive effect on blood pressure regulation, and there aren’t any medications to modulate the mechanism.”

In the study, 23 elderly patients diagnosed and treated for hypertension were randomly allocated into two groups: morning training and evening training. Both groups trained for ten weeks on a stationary bicycle at moderate intensity, with three 45-minute sessions per week.

Key cardiovascular parameters were analysed, such as systolic and diastolic blood pressure, and heart rate after ten minutes’ rest. The data was collected before and at least three days after the volunteers completed the ten weeks of training.

The researchers also monitored mechanisms pertaining to the autonomic nervous system, which controls breathing, heart rate, blood pressure, digestion, and other involuntary bodily functions, such as muscle sympathetic nerve activity, which regulates peripheral blood flow via contraction and relaxation of blood vessels in muscle tissue, and sympathetic baroreflex sensitivity, assessing control of blood pressure via alterations to muscle sympathetic nerve activity.

In the evening training group, all four parameters analysed were found to improve: systolic and diastolic blood pressure, sympathetic baroreflex sensitivity, and muscle sympathetic nerve activity. In the morning training group, no improvements were detected in muscle sympathetic nerve activity, systolic blood pressure or sympathetic baroreflex sensitivity.

“Evening training was more effective in terms of improving cardiovascular autonomic regulation and lowering blood pressure. This can be partly explained as due to an improvement in baroreflex sensitivity and a reduction of muscle sympathetic nerve activity, which increased in the evening. For now, all we know is that baroreflex control is the decisive factor, from the cardiovascular standpoint at least, to make evening training more beneficial than morning training, since it induces the other benefits analysed. However, much remains to be done in this regard in order to obtain a better understanding of the mechanisms involved,” said Brito, who is currently a professor at Oregon Health & Science University’s Oregon Institute of Occupational Health Sciences in the United States, and continues to investigate the topic via circadian rhythm studies.

Baroreflex sensitivity regulates each heartbeat interval and controls autonomic activity throughout the organism.

“It’s a mechanism that involves sensitive fibres and deformations in the walls of arteries in specific places, such as the aortic arch and carotid body. When blood pressure falls, this region warns the brain region that controls the autonomic nervous system, which in turn signals the heart to beat faster and tells the arteries to contract more strongly. If blood pressure rises, it warns the heart to beat more slowly and tells the arteries to contract less. In other words, it modulates arterial pressure beat by beat,” Brito explained.

In previous studies, the EEFE-USP research group showed that evening aerobic training reduced blood pressure more effectively than morning training in hypertensive men (read more at: agencia.fapesp.br/34194), and that the more effective response to evening training in terms of blood pressure control was accompanied by a greater reduction in systemic vascular resistance and systolic pressure variability (read more at: agencia.fapesp.br/37432).

“Replication of the results obtained in previous studies and in different groups of hypertensive patients, associated with the use of more precise techniques to evaluate the main outcomes, has strengthened our conclusion that aerobic exercise performed in the evening is more beneficial to the autonomic nervous system in patients with hypertension. This can be especially important for those with resistance to treatment with medication,” Brito said.

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

A new hybrid nanotube stamp system has been developed which revolutionises precision medicine with high efficiency and cell viability rates for cancer treatment.

Precision medicine and targeted therapies are gaining traction for their ability to tailor treatments to individual patients while minimising adverse effects. Conventional methods, such as gene transfer techniques, show promise in delivering therapeutic genes directly to cells to address various diseases.

However, these methods face significant drawbacks, hindering their efficacy and safety. Intracellular protein delivery offers a promising approach for developing safer, more targeted, and effective therapies. By directly transferring proteins into target cells, this method circumvents issues such as silencing during transcription and translation and the risk of undesirable mutations from DNA insertion. Additionally, intracellular protein delivery allows for precise distribution of therapeutic proteins within target cells without causing toxicity.

A group of researchers led by Professor Takeo Miyake at Waseda University, Japan in collaboration with the Mikawa Group at the RIKEN Institute have now developed a hybrid nanotube stamp system for intracellular delivery of proteins. This innovative technique enables the simultaneous delivery of diverse cargoes, including calcein dye, lactate oxidase (LOx) enzyme, and ubiquitin (UQ) protein, directly into adhesive cells for cancer treatment.

The researchers explored the therapeutic potential of delivering LOx enzyme for cancer treatment. “Through our innovative stamp system, we successfully delivered LOx into both healthy mesenchymal stem cells (MSC) and cancerous HeLa cells. While MSC cells remained unaffected, we observed significant cell death in HeLa cancer cells following LOx treatment with viabilities decreasing over time. Our findings highlight the promising efficacy of intracellularly delivered LOx in selectively targeting and killing cancer cells, while sparing healthy cells, offering a targeted therapeutic strategy for cancer treatment,” explains Miyake.

Finally, the team successfully delivered 15N isotope-labeled UQ proteins into HeLa cells using the HyNT stamp system. This delivery allowed for the analysis of complex protein structures and interactions within the cells. In addition, optical and fluorescence imaging confirmed the presence of delivered UQ in HeLa cells, and nuclear magnetic resonance spectroscopy matched the intracellular UQ protein concentration with that of a solution containing 15N-labeled UQ. These results demonstrate the effectiveness of the stamp system in delivering target proteins for subsequent analysis.

The results demonstrate the remarkable capability of the HyNT stamp system in delivering LOx and UQ into a substantial number of adhesive cells, as required for regenerative medicine applications. The system achieved a notably high delivery efficiency of 89.9%, indicating its effectiveness in transporting therapeutic proteins into the target cells with precision. Moreover, the cell viability rate of 97.1% highlights the system’s ability to maintain the health and integrity of the treated cells throughout the delivery process.

The HyNT stamp system offers transformative potential in intracellular protein delivery, with applications spanning from cancer treatment to molecular analysis. Beyond medicine, its versatility extends to agriculture and food industries, promising advancements in crop production and food product development. With precise cell manipulation and efficient delivery, the HyNT stamp system is poised to revolutionize biomedical research, clinical practice, and diverse industries, paving the way for personalized interventions and shaping the future of modern medicine.

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Heat waves damage humans’ vital organs, shows new study

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Researchers from the University of California, Irvine have found evidence of the molecular causes of the damaging impact heat stress causes on the gut, liver and brain in the elderly.

The researchers suggest these findings point to the potential of developing precise prognostic and therapeutic interventions.

These organs have a complex and multidirectional communication system that touches everything from our gastrointestinal tract to the nervous system. Whether it is our brain affecting hunger or the liver influencing mental health, understanding the gut-liver-brain communication or “axis” is crucial to protecting human health.

Their study, which was conducted on mouse models, is published in the journal Scientific Reports, a Nature Portfolio journal. It is one of the first to fill the knowledge gap on the effects of heat stress on a molecular level of this crucial biological conversation.

“Inflammation in the brain and spine contributes to cognitive decline, compromises the ability to form new neurons and exacerbates age-related diseases,” said corresponding author, Saurabh Chatterjee, a professor of environmental & occupational health at the UC Irvine Program in Public Health. “By investigating the effects of heat stress on the gut-liver-brain crosstalk, we can better protect our increasingly vulnerable aging population.”

Using RNA analysis and bioinformatics to analyse elderly, heat-stressed mice, Chatterjee and his team found evidence of heat stress-affected genes in the brain and liver. A significant increase in the production of ORM2, a liver-produced protein, was observed in the heat-stressed mice. The control group of unstressed mice did not show a change, providing proof of organ dysfunction in the heat-stressed mice.

Researchers believe that increased secretion of ORM2 is a coping mechanism that may be due to gut inflammation and imbalance. In addition, ORM2 may impact the brain through a leaky blood-brain barrier, emphasizing intricate multi-organ crosstalk.

Additionally, the study shows the potential to use ORM2 for targeted biomarker interventions to prevent liver disease in heat exposure. This observation advances molecular insights into the pathophysiology of adverse heat events and will serve as a foundation for future research.

“Our findings have the potential to be used for the development of prognostic and therapeutic markers for precise interventions,” said Chatterjee. “In a dynamically changing global landscape, the imminent threat of climate change is evident in rising temperatures, raising concerns about intermittent heat waves. Our heating planet is undoubtedly leading to acute and chronic heat stress that harms the health of our aging population.”

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