New microscope offers faster, high-resolution brain imaging

The new two-photon fluorescence microscope that captures high-speed images of neural activity at cellular resolution. By imaging much faster and with less harm to brain tissue than traditional two-photon microscopy, it could provide a clearer view of how neurons communicate in real time, leading to new insights into brain function and neurological diseases.

"The microscope is ideally suited for studying the dynamics of neural networks in real time, which is crucial for understanding fundamental brain functions such as learning, memory and decision-making," For example, it could use it to observe neural activity during learning to better understand communication and interaction among different neurons during this process."

which incorporates a new adaptive sampling scheme and replaces traditional point illumination with line illumination. They show that the new method enables in vivo imaging of neuronal activity in a mouse cortex and can image at speeds ten times faster than traditional two-photon microscopy while also reducing the laser power on the brain more than tenfold.

"This could help for better understand and more effectively treat neurological diseases such as Alzheimer's, Parkinson's and epilepsy."

High-speed imaging with less damage

Two-photon microscopy can image deep into scattering tissue such as a mouse brain by scanning a small point of light across the entire sample area to excite fluorescence and then collecting the resulting signal point by point. This process is then repeated to capture each imaging frame. Although two-photon microscopy provides detailed images, it is slow and can damage brain tissue.

It aimed to overcome these limitations through a new sampling strategy. Rather than using a point of light, they use a short line of light to illuminate specific parts of the brain where neurons are active. This enables a larger area to be excited and imaged at once, thus speeding up the imaging process significantly. Also, because it only images neurons of interest -- not the background or inactive areas -- the total light energy deposited to the brain tissue is reduced, lowering the risk for potential damage. They called this scheme adaptive sampling.

This accomplished this by using a digital micromirror device (DMD) -- a chip containing thousands of tiny mirrors that can be individually controlled -- to dynamically shape and steer the light beam, enabling precise targeting of active neurons. They achieved adaptive sampling by turning individual DMD pixels on and off in a way that adjusts to the neuronal structure of the brain tissue being imaged.

They also developed a technique to use the DMD to mimic high-resolution point scanning. This allows a high-resolution image to be reconstructed from fast scans, providing a quick way to identify neuronal regions of interest. This is critical for the subsequent high-speed imaging with the short-line excitation and adaptive sampling scheme.

"These developments -- each crucial on its own -- come together to create a powerful imaging tool that significantly advances the ability to study dynamic neural processes in real time, with reduced risk to living tissue," said Yang. "Importantly, our technique can be combined with other techniques like beam multiplexing and remote focusing to further increase the imaging speed or to achieve volumetric 3D imaging."

Capturing neural activity

They demonstrated the new microscope by using it to image calcium signals -- indicators of neural activity -- in living mouse brain tissue. The system captured these signals at a speed of 198 Hz, which is significantly faster than traditional two-photon microscopes and demonstrates the ability to monitor rapid neuronal events that would be missed by slower imaging methods.

They also showed that the adaptive line-excitation technique coupled with advanced computational algorithms makes it possible to isolate the activity of individual neurons. This is important for accurately interpreting complex neural interactions and understanding the functional architecture of the brain.

Next, they are working to integrate voltage imaging capabilities into the microscope to capture a direct and extremely rapid readout of neural activity. They also plan to use the new method for real neuroscience applications, such as observing neural activity during learning and studying brain activity in disease states. Additionally, they aim to improve the microscope's user-friendliness and reduce its size to enhance its utility in neuroscience research.

Reference:

Yunyang Li, Shu Guo, Ben Mattison, Junjie Hu, Kwun Nok Mimi Man, Weijian Yang. High-speed two-photon microscopy with adaptive line-excitation. Optica, 2024; 11 (8): 1138 DOI: 10.1364/OPTICA.529930

 

A healthy lifestyle may counteract diabetes-associated brain aging

 

Type 2 diabetes is a known risk factor for dementia, but it is unclear how diabetes and its early stages, known as prediabetes, affect brain ageing in people without dementia. Now, a comprehensive brain imaging study shows that both diabetes and prediabetes can be linked to accelerated brain ageing.

 

The study included more than 31,000 people between 40 and 70 years of age from the UK Biobank who had undergone a brain MRI scan (magnetic resonance imaging).

 

The researchers used a machine learning approach to estimate brain age in relation to the person's chronological age. Prediabetes and diabetes were associated with brains that were 0.5 and 2.3 years older than chronological age, respectively. In people with poorly controlled diabetes, the brain appeared more than four years older than chronological age.

 

The researchers also noted that the gap between brain age and chronological age increased slightly over time in people with diabetes. These associations were attenuated among people with high physical activity who abstained from smoking and heavy alcohol consumption.

 

"Having an older-appearing brain for one's chronological age can indicate deviation from the normal ageing process and may constitute an early warning sign for dementia," says the study. "On the positive side, it seems that people with diabetes may be able to influence their brain health through healthy living."

 

Repeated MRI data were available for a small proportion of the study participants. Follow-up MRI scans are ongoing and researchers are now continuing to study the association between diabetes and brain ageing over time. "There's a high and growing prevalence of type 2 diabetes in the population,". "We hope that our research will help prevent cognitive impairment and dementia in people with diabetes and prediabetes." 

 Reference:

Abigail Dove, Jiao Wang, Huijie Huang, Michelle M. Dunk, Sakura Sakakibara, Marc Guitart-Masip, Goran Papenberg, Weili Xu. Diabetes, Prediabetes, and Brain Aging: The Role of Healthy Lifestyle. Diabetes Care, 2024; DOI: 10.2337/dc24-0860

 

Treating Radiation Wounds with Aspirin Hydrogels

Radiation is a powerful tool for treating cancer, but prolonged exposure can damage the skin. 

Radiation-induced skin injuries are painful and increase a person's chances of infection and long-term inflammation. 

Researchers in ACS Biomaterials Science & Engineering report an aspirin-containing hydrogel that mimics the nutrient-rich fluid between cells and accelerates healing of skin damaged by radiation in animals. With further development, the new salve could provide effective and rapid wound healing for humans.

People undergoing radiotherapy for cancer will experience radiation-induced skin injury that can include redness, pain, ulcers, necrosis and infection.

There are few treatments for these wounds, with the most common methods being debridement (surgical removal of the damaged skin) and hyperbaric oxygenation (exposure to pure oxygen in a pressurized environment). 

Wound dressings made from hydrogels are gaining popularity because they are easy to apply and provide a wet environment for healing that is similar to the inside of the body.

Glycopeptide-based hydrogels are especially promising: In laboratory and animal studies, the nanofiber structures have promoted cellular growth and regulated cell adhesion and migration.

A research team led by Jiamin Zhang, Wei Wang, Yumin Zhang and Jianfeng Liu proposed loading aspirin, a common anti-inflammatory drug, into a glycopeptide-based hydrogel to create a multifunctional wound dressing for radiation-induced skin injuries.

In lab tests with cultured cells, the researchers found that the aspirin-contained hydrogel scavenged reactive oxygen species, repaired DNA double-strand breaks and inhibited inflammation caused by radiation exposure without affecting cellular growth. 

In mouse models of radiation-induced skin injury, the researchers found that dressing wounds for three weeks with the salve reduced acute injuries and accelerated healing -- results that the team says point to its potential as an easy-to-administer, on-demand treatment option for reducing radiation damage and promoting healing in humans.

Reference:

Jiajun Guo, Xiaoguang Zhang, Ruiqi Mao, Hui Li, Yusen Hao, Jiamin Zhang, Wei Wang, Yumin Zhang, Jianfeng Liu. Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury. ACS Biomaterials Science & Engineering, 2024; 10 (8): 5168 DOI: 10.1021/acsbiomaterials.4c00698

Low Magnesium Levels Increase Disease Risk

A diet rich in magnesium is so important for our health, reducing the risk of DNA damage and chronic degenerative disorders.

Scientists from the University of South Australia measured blood samples from 172 middle aged adults, finding a strong link between low magnesium levels and high amounts of a genotoxic amino acid called homocysteine.

This toxic combination damages the body's genes, making people more susceptible to Alzheimer's and Parkinson's disease, gastrointestinal diseases, a range of cancers, and diabetes.

Whole grains, dark green leafy vegetables, nuts, beans and dark chocolate are all magnesium-rich foods, which help the body produce energy, build teeth and bones, regulate blood sugar and blood pressure, and ensure that the heart, muscles and kidneys all work properly.

UniSA molecular biologist Dr Permal Deo says a low intake of magnesium (less than 300mg per day) can increase the risk of many diseases, but its role in preventing DNA damage has not been fully studied in humans until now.

"Our study showed a direct correlation between low magnesium levels in blood (less than 18mg/L) and increased DNA damage, even after adjusting for gender and age," Dr Deo says.

"Blood levels of magnesium, homocysteine (Hcy), folate and vitamin B12 were measured, showing an inverse correlation between magnesium and Hcy and a positive correlation between magnesium, folate and vitamin B12. 

This indicates that sufficiently high magnesium levels in the blood are essential to protect our genes from toxicity caused by homocysteine, which is increased when folate and vitamin B12 are deficient."

Co-author Professor Michael Fenech says chronic magnesium deficiency is likely to disrupt the body's ability to produce energy and power cells, causing accelerated tissue ageing and making people more susceptible to early onset of many diseases.

Magnesium is the fourth most abundant mineral present in the human body.

More than 600 enzymes require it as a co-factor and almost 200 require it to activate critical processes in the body.

"The next step is to determine the optimal dietary intake of magnesium, either through food or supplements and how this could impact the onset or progression of cancer and other chronic diseases," Prof Fenech says..

 

 

Reference: 

Varinderpal S. Dhillon, Permal Deo, Michael Fenech. Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians. European Journal of Nutrition, 2024; DOI: 10.1007/s00394-024-03449-0

First pill for dengue shows promise in human challenge trial

First pill for dengue shows promise in human challenge trial

The positive early data supports ongoing Phase II trials of the pill to prevent the four different types of dengue in a real world-setting.

“It is the first ever to show antiviral activity against dengue,” Marnix Van Loock, who oversees emerging pathogens research for J&J’s Janssen division, said of the drug.

In human challenge trials, researchers intentionally expose healthy volunteers to a pathogen to test a vaccine or treatment, or better understand the disease they cause.

Dengue fever, while often asymptomatic, is also known as “break bone fever” for the severity of the joint pain and spasms that some patients experience. It has long been a scourge across much of Asia and Latin America, causing millions of infections each year and tens of thousands of deaths, and is likely to spread further as climate change makes more areas hospitable for the mosquitoes that spread it, the World Health Organization’s chief scientist Jeremy Farrar said earlier this month.

In the trial done with Johns Hopkins Bloomberg School of Public Health, 10 volunteers were given a high dose of the J&J pill five days before being injected with a type of dengue. They continued to take the pill for 21 days afterwards.

Six of the 10 showed no detectable dengue virus in their blood after being exposed to the pathogen, as well as no signs that their immune system had responded to infection by the virus over 85 days of monitoring.

The five people in a placebo group, who were also injected with dengue, all showed detectable virus when tested. Trial participants received standard care from medical professionals where necessary, and the virus used was a weakened version to minimise symptoms.

Scientists create human embryo in lab without eggs, sperm

Scientists create human embryo in the lab without eggs, sperm

The models accurately emulated embryonic development in its earliest stages - a process still poorly understood due to ethical constraints on real embryo research.

A stem cell–derived human embryo model at a developmental stage equivalent to that of a day 14 embryo.

In a scientific first, researchers at Israel's Weizmann Institute of Science have successfully created synthetic models of 14-day-old human embryos derived entirely from stem cells grown in a lab.

The breakthrough, reported in the journal Nature, provides an unprecedented glimpse into the mysterious earliest stages of human development and could open up new avenues of research into infertility, birth defects, and organ growth.

Led by molecular biologist Professor Jacob Hanna, the Weizmann team started with two types of stem cells - those reprogrammed from adult skin cells and others derived from established lab-grown stem cell lines.

Using a specialised technique developed by Hanna in 2013, they reverted the cells to an earlier, more flexible “naive” state resembling a 7-day-old embryo ready for implantation.

 Industrial Visit 

VANITECLIMITED

  Common Effluent Treatment Plant

Vaniyambadi, Tamil Nadu.

BACKGROUND

Vanitec Limited was incorporated in the year 1986 with the aim of providing wastewater treatment utilities for the benefit of its member-tanneries. The Company services the wastewater treatment needs of its 134 member-tanneries through a Common Effluent Treatment Plant (CETP) located in Valayampet, Vaniyambadi.

The Company was a pioneer in setting-up the first CETP for clusters of tanneries in India and commissioned the plant in May 1991 that continues to be in operation till date.

The Board oversees the day-to-day operation and maintenance of the Common Effluent Treatment Plants through a Plant Manager who has an able team of qualified engineers and chemists supervising a dedicated group of electrical, instrumentation, process and mechanical engineers alongwith general workmen operating on a 24-7-365 schedule. Administrative and accounting staff are available to take care of documentation and billings and the total personnel strength is 100.

PROCESS - FROM 1991 TO 2013

Wastewater treatment was based on a 2-stage process comprising of a Primary & Secondary treatment system. In the Primary Treatment, coarse debris and suspended solids were removed from the wastewater and the remaining dissolved organics were degraded in a biological treatment phase that used a consortia of a bacteria that brought about the wastewater to a condition that was suitable for river discharge

PROCESS - FROM 2013 ONWARDS

With the implementation of the Zero Liquid Discharge System, the Common Effluent Treatment Plant has stopped the discharge of its effluent into the River Palar. The wastewater is treated through a 4-Stage process whereby the water is completely recovered and reused by its member-tanneries and crystalline salt is recovered and stored for safe disposal. The 4-Stage process comprises of the following components -

- Primary Stage
- For removal of coarse debris and suspended solids
- Secondary Stage
- For the degradation of dissolved organics in the wastewater and thereby making it relatively benign
- Based on Membrane Bio Reactor technology
- Tertiary Stage
- Removal of remnant dissolved inorganics and organics and delivering 70% of very clean water that measure up to drinking water standards
- Final Stage
- Evaporation of 30% of the balance of �rejects� in a multiple-effect evaporator for crystallization of the inorganic salts that would go for storage or for possible reuse

FINANCIAL BACKGROUND

As stated earlier, the Company was a pioneer in setting-up the first CETP for clusters of tanneries in India. Keeping this in mind, the Central Pollution Control Board, New Delhi invested Rs.10 lakhs in the equity of the Company. As it was a demonstration plant for tanneries in India, the Ministry of Industry, Government of India supported the effort with a special subsidy of Rs.15 lakhs. Matching grants were given by the Government of Tamil Nadu, which allocated a sum of Rs.25 lakhs as it was to be a concept-demonstrator. Apart from such participation, the Company received subsidies from the Central and State Governments to the extent of Rs.141.25 lakhs. The remaining funds were contributed by the member-tanneries that stood at Rs.145.75 lakhs. When the plant was commissioned in 1991, the capital investment stood at Rs.337 lakhs.
Between 1992 & 2004, further investments required for the modernization of the CETP took up the Gross Block of the Company to Rs.9.00 crores.

To comply with the mandated norm of Zero Liquid Discharge by the Tamil Nadu Pollution Control Board in the year 2004, the Company embarked upon the full-scale upgradation of its Common Effluent Treatment Plant.

The Water Recovery & Reuse Project was established at a cost of Rs.62.00 crores and was funded through a grant (35% of the project cost) from the Industrial Infrastructure Upgradation Scheme sponsored by the Department of Policy & Promotion, Ministry of Commerce & Industry, New Delhi while the balance of 65% being sourced from the beneficiary members and financial institution/s.

In 2012, the Company installed a Cross-Flow MBR at a cost Rs.6.00 Crores and further is in the process of erecting and commissioning an 8-Stage Multiple-Effect Evaporator at a cost of Rs.19.00 crores. This investment of Rs.25.00 crores has come solely from the pockets of the tanneries thus resulting in the total cost of the ZLD plant at Rs.87.00 crores and the cumulative cost of the project to Rs.96.00 crores.