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Comment by Dr. Krishna Kumari Challa on January 3, 2024 at 8:36am

Through rational and machine learning-guided optimization over several rounds of experiments, the team was able to improve the acetyl-CoA yield by a factor of 100. In order to test its in vivo feasibility, incorporation into the living cell should be carried out step by step.

To this end, the researchers divided the THETA cycle into three modules, each of which was successfully implemented into the bacterium E. coli. The functionality of these modules was verified through growth-coupled selection and/or isotopic labeling.

What is special about this cycle is that it contains several intermediates that serve as central metabolites in the bacterium's metabolism. This overlap offers the opportunity to develop a modular approach for its implementation.
Bringing parts of the THETA cycle into living cells is an important proof-of-principle for synthetic biology.

Shanshan Luo et al, Construction and modular implementation of the THETA cycle for synthetic CO₂ fixation, Nature Catalysis (2023). DOI: 10.1038/s41929-023-01079-z

Part 2

Comment by Dr. Krishna Kumari Challa on January 3, 2024 at 8:33am

 Synthetic carbon dioxide fixation in living cells

Synthetic biology offers the opportunity to build biochemical pathways for the capture and conversion of carbon dioxide (CO₂). Researchers have developed a synthetic biochemical cycle that directly converts CO₂ into the central building block Acetyl-CoA.

The researchers were able to implement each of the three cycle modules in the bacterium E.coli, which represents a major step towards realizing synthetic CO2 fixing pathways within the context of living cells.
Developing new ways to capture and convert CO2 is key to tackling the climate emergency. Synthetic biology opens avenues for designing new-to-nature CO2-fixation pathways that capture CO2 more efficiently than those developed by nature.

However, realizing those new-to-nature pathways in different in vitro and in vivo systems is still a fundamental challenge. Researchers have now designed and constructed a new synthetic CO2-fixation pathway, the so-called THETA cycle.

It contains several central metabolites as intermediates and has the central building block, acetyl-CoA, as its output. This characteristic makes it possible to be divided into modules and integrated into the central metabolism of E. coli.

The entire THETA cycle involved 17 biocatalysts and was designed around the two fastest CO2-fixing enzymes known to date: crotonyl-CoA carboxylase/reductase and phosphoenolpyruvate carboxylase.

The researchers found these powerful biocatalysts in bacteria. Although each of the carboxylases can capture CO2 more than ten times faster than RubisCO, the CO2-fixing enzyme in chloroplasts, evolution itself has not brought these capable enzymes together in natural photosynthesis.

The THETA cycle converts two CO2 molecules into one acetyl-CoA in one cycle. Acetyl-CoA is a central metabolite in almost all cellular metabolism and serves as the building block for a wide array of vital biomolecules, including biofuels, biomaterials, and pharmaceuticals, making it a compound of great interest in biotechnological applications. Upon constructing the cycle in test tubes, the researchers could confirm its functionality.
Part 1

Comment by Dr. Krishna Kumari Challa on January 3, 2024 at 8:26am

The results showed that when light hits the retina, visual areas of the brain respond by increasing their activity to represent the pattern of light. Memory areas of the brain also respond to visual stimulation, but, unlike visual areas, their neural activity decreases when processing the same visual pattern.

The researchers report that the study has three unusual findings. The first is their discovery that a visual coding principle is preserved in memory systems.

The second is that this visual code is upside-down in memory systems. When you see something in your visual field, neurons in the visual cortex are driving while those in the memory system are quieted.

Third, this relationship flips during memory recall. If you close your eyes and remember that visual stimuli in the same space, you'll flip the relationship: your memory system will be driving, suppressing the neurons in perceptual regions.

These results provide a clear example of how shared visual information is used by memory systems to bring recalled memories in and out of focus.

Adam Steel et al, A retinotopic code structures the interaction between perception and memory systems, Nature Neuroscience (2024). DOI: 10.1038/s41593-023-01512-3

Part 2

Comment by Dr. Krishna Kumari Challa on January 3, 2024 at 8:24am

Researchers identify new coding mechanism that transfers information from perception to memory

Our memories are rich in detail: we can vividly recall the color of our home, the layout of our kitchen, or the front of our favorite café. How the brain encodes this information has long puzzled neuroscientists.

In a new study, researchers identified a neural coding mechanism that allows the transfer of information back and forth between perceptual regions to memory areas of the brain. The results are published in Nature Neuroscience.

The researchers found that memory-related brain areas encode the world like a 'photographic negative' in space. And that 'negative' is part of the mechanics that move information in and out of memory, and between perceptual and memory systems.

In a series of experiments, participants were tested on perception and memory while their brain activity was recorded using a functional magnetic resonance imaging (fMRI) scanner. The team identified an opposing push-pull like coding mechanism, which governs the interaction between perceptual and memory areas in the brain.

Part 1

Comment by Dr. Krishna Kumari Challa on January 3, 2024 at 7:26am

Closing in on the ultimate quest to regenerate insulin in pancreatic stem cells

Researchers are zeroing in on the ultimate quest to regenerate insulin in pancreatic stem cells and replace the need for regular insulin injections.

researchers have demonstrated in an article published in Signal Transduction and Targeted Therapy that newly made insulin cells can respond to glucose and produce insulin following stimulation with two approved drugs in as little as 48 hours.

Further, they confirmed this pathway of awakening the insulin-producing cells is viable in age groups from 7 to 61, providing much-needed insights into the mechanisms underlying the regeneration of beta cells.

Using pancreatic cells derived from a child and adult type 1 diabetic donors, and from a non-diabetic person, a research  team demonstrated how insulin-producing cells that are destroyed in people with type 1 diabetes can be regenerated into glucose sensing and functionally secreting insulin cells. In this latest study by the Human Epigenetics team, they show small molecule inhibitors that are currently used for rare cancers and approved  can rapidly return insulin production in pancreatic cells destroyed by diabetes. While current pharmaceutical options for diabetes treatment help control blood glucose levels they do not prevent, stop or reverse the destruction of insulin-secreting cells.

The novel therapeutic approach holds the potential to become the first disease modifying treatment for type 1 diabetes by facilitating glucose responsive insulin production by harnessing the patient's remaining pancreatic cells, thereby enabling people living with diabetes to potentially achieve independence from round-the-clock insulin injections.

This disease-modifying treatment also represents a promising solution for the significant number of people living with insulin dependent diabetes, who account for 30% of those with type 2 diabetes.

 Keith Al-Hasani et al, EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors, Signal Transduction and Targeted Therapy (2024). DOI: 10.1038/s41392-023-01707-x

Comment by Dr. Krishna Kumari Challa on January 2, 2024 at 9:43am

Disorders, diseases associated with childlessness identified

Mental-behavioral disorders, congenital anomalies, and endocrine-nutritional-metabolic disorders are most strongly associated with childlessness, according to a study published online Dec. 18 in Nature Human Behaviour.

Researchers examined 1,035,928 men born in 1956 to 1968 and women born in 1956 to 1973 in Finland and 1,509,092 born in Sweden to the completion of their reproductive lifespan in 2018. Using a population and matched-pair case-control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers), sociodemographic and reproductive information was associated with 414 diseases across 16 categories.

The researchers found the associations were strongest for mental-behavioral disorders (especially among men), congenital anomalies, and endocrine-nutritional-metabolic disorders (strongest among women). New associations were identified for inflammatory and autoimmune diseases. The associations were dependent on age at onset; singlehood and education were mediators of the associations.

Researchers have comprehensively described the associations between different diseases, particularly those with onset prior to the peak reproductive age, and the chance of being childless over a lifetime. 

 Aoxing Liu et al, Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women, Nature Human Behaviour (2023). DOI: 10.1038/s41562-023-01763-x

Comment by Dr. Krishna Kumari Challa on December 30, 2023 at 10:02am

Food-as-medicine programs are gaining popularity, with variations like produce prescription programs and medically tailored meals. The current study may hint that a short-term intervention diet is insufficient in creating clinically measurable change and that longer-term food and nutrition security is required.

More information: Joseph Doyle et al, Effect of an Intensive Food-as-Medicine Program on Health and Health Care Use, JAMA Internal Medicine (2023). DOI: 10.1001/jamainternmed.2023.6670

Deborah Grady, Food for Thought—Include Controls in Policy Evaluations, JAMA Internal Medicine (2023). DOI: 10.1001/jamainternmed.2023.6659

Part 3

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Comment by Dr. Krishna Kumari Challa on December 30, 2023 at 10:02am

Access to the program did increase engagement with preventive health care. More dietitian visits, active prescription drug orders, and self-reported improved diets were noted in the treatment group. These increases did not result in improved glycemic control compared to usual care with food insecurity.

No significant differences between treatment and control were observed in cholesterol, triglycerides, fasting glucose, or blood pressure at six or 12 months. It is unclear why a healthy and secure diet and increased access to medical professionals had no effect on any of these measures in the study.

The study seems to show that the damage caused by prolonged food insecurity is not easily reversible. It also suggests that any effort to assist people struggling with food insecurity and diabetes cannot be helped by diet alone.

According to the Centers for Disease Control, people who experience food and nutrition insecurity are two to three times more likely to have diabetes than people who do not. Healthy eating is essential for managing blood sugar levels and can help prevent type 2 diabetes.

Nutritious foods can be expensive or difficult to find for individuals living below the poverty level, often leaving them dependent on calories from highly processed food sources. For people who already have diabetes, buying healthy foods can compete with health care expenses for medicines, devices, and supplies, creating a dire "treat" or "eat" scenario.

While the study found no significant short-term improvements in the subjects recruited for the study, the problem of food and nutrition insecurity is rising along with a rise in diet-related chronic diseases.
Part 2

Comment by Dr. Krishna Kumari Challa on December 30, 2023 at 10:02am

Food-as-Medicine study finds no improvements in type 2 diabetes patients

Recent research has found that an intensive food-as-medicine program showed no improvement in glycemic control in patients with type 2 diabetes and food insecurity.

In their paper, "Effect of an Intensive Food-as-Medicine Program on Health and Health Care Use—A Randomized Clinical Trial," published in JAMA Internal Medicine, a research team details a randomized clinical trial  of 349 type 2 diabetes patients with previous food insecurity to assess if short-term access to healthy food options could improve glycemic control and influence health care usage.

The study targeted patients with type 2 diabetes and elevated HbA1c levels, providing intensive support and food supplies. Subjects in the treatment group (n=170) were given groceries for 10 healthy meals per week for the household, dietitian consultations, nurse evaluations, health coaching, and diabetes education for one year with a one-year follow-up. A control group (n=179) did not receive any of the benefits of the treatment program for the first six months. Hemoglobin A1C (HbA1c) tests six months into the program showed substantial declines in both the treatment (1.5%) and control (1.3%) groups, resulting in no significant difference between groups. This might indicate that factors beyond the program contributed to the lower blood sugar levels, though what these factors might be is unclear.

Part 1

Comment by Dr. Krishna Kumari Challa on December 29, 2023 at 12:46pm

Other methods of translating brain signals into language require invasive surgeries to implant electrodes or bulky, expensive MRI machines, making them impractical for daily use – and they often need to use eye-tracking to convert brain signals into word-level chunks.

When a person's eyes dart from one word to another, it's reasonable to assume that their brain takes a short break between processing each word. Raw EEG wave translation into words – without eye tracking to indicate the corresponding word target – is harder.

Brain waves from different people don't all represent breaks between words quite the same way, making it a challenge to teach AI how to interpret individual thoughts.

After extensive training, DeWave's encoder turns EEG waves into a code that can then be matched to specific words based on how close they are to entries in DeWave's 'codebook'.

"It is the first to incorporate discrete encoding techniques in the brain-to-text translation process, introducing an innovative approach to neural decoding," explain the researchers.

The integration with large language models is also opening new frontiers in neuroscience and AI.

https://arxiv.org/abs/2309.14030

Part 2

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