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Comment by Dr. Krishna Kumari Challa on January 24, 2023 at 10:52am

Novel method helps recover obscured images

A novel method that produces a clear image by using a simple cost-effective random scattering medium in real time could help overcome problems of obscured images.

When light passes through a light-scattering material, it is diffused rather than absorbed, which means a clear image of the source object is lost. Scattering media include clouds, which poses problems for Earth-based astronomy, and body tissue, which affects medical imaging.

Previous methods for reconstructing scattered light have required some initial knowledge of the object and the ability to control the wavefront of light illuminating it. This has involved complicated optical elements and high vulnerability to motion and mechanical instability. Computational algorithms are then able to post-process the detected light to generate an image.

To get more efficient ways of reconstruction, speckle-correlation imaging was proposed. This extracts information about the source from fluctuations in the intensity, or speckles, in the transmitted light.

However, many of the technologies based on speckle-correlation need time-consuming and intricately calibrated computational reconstruction. Also, still missing is some information such as the image orientation and location.

Now researchers have developed a way to directly obtain a clear image from a single shot of the speckle image.

They passed light from a small standardized test object through a thin diffusing material. By moving a camera in a direction away from the diffuser, they were able to build a three-dimensional image, taking slices through the speckles.

By looking at enlarged sections of these images, the researchers, to their surprise, could directly see reproductions of the test object; they could see through the random diffuser with the naked eye and real-time video imaging. It required no complex equipment for the active control of light nor prior knowledge of the source or diffusion medium. They could also find the lost orientation information and location of the test object.

Jietao Liu et al, Directly and instantly seeing through random diffusers by self-imaging in scattering speckles, PhotoniX (2023). DOI: 10.1186/s43074-022-00080-2

Comment by Dr. Krishna Kumari Challa on January 24, 2023 at 10:38am

Study reveals new genetic disorder that causes susceptibility to opportunistic infections

Researchers have discovered a new genetic disorder that causes immunodeficiency and profound susceptibility to opportunistic infections including a life-threatening fungal pneumonia.

The discovery, reported Jan. 20 in the journal Science Immunology, will help identify people who carry this in-born error of immunity (IEI).

IEIs, also known as primary immunodeficiencies, are genetic defects characterized by increased susceptibility to infectious diseases, autoimmunity, anti-inflammatory disorders, allergy, and in some cases, cancer.

To date, 485 different IEIs have been identified. It is now thought that they occur in one of every 1,000 to 5,000 births, making them as prevalent as other genetic disorders, including cystic fibrosis and Duchene's muscular dystrophy.

Despite recent medical advances, about half of patients with IEIs still lack a genetic diagnosis that could help them avoid debilitating illness and death. This new work helps with that. 

The error in this case is a mutation in the gene for the protein IRF4, a transcription factor that is pivotal for the development and function of B and T white blood cells, as well as other immune cells.

The researchers sequenced the protein-encoding regions of a boy's - who was suffering from severe and recurrent fungal, viral, mycobacterial, and other infections -  genome  and discovered a de novo IRF4 mutation, which originated in the patient and was not inherited from his parents.

In the current study, the researchers identified seven patients from six unrelated families across four continents with profound combination immunodeficiency who experienced recurrent and serious infections, including pneumonia caused by the fungus Pneumocystis jirovecii. Each patient had the same mutation in the DNA-binding domain of IRF4.

Extensive phenotyping of patients' blood cells revealed immune cell abnormalities associated with the disease, including impaired maturation of antibody-producing B cells, and reduced T-cell production of infection-fighting cytokines.

Two knock-in mouse models, in which the mutation was inserted into the mouse genome, exhibited a severe defect in antibody production consistent with the combined immune deficiency observed in the patients.

The researchers also discovered the mutation had a "multimorphic" effect detrimental to the activation and differentiation of immune cells.

While the mutant IRF4 binds to DNA with a higher affinity than the native form of the protein (in a hypermorphic way), its transcriptional activity in common, canonical genes is reduced (hypomorphic), and it binds to other DNA sites (in a neomorphic way), altering the protein's normal gene expression profile.

This multimorphic activity is a new mechanism for human disease. "We anticipate that variants with multimorphic activity may be more widespread in health and disease," the researchers concluded.

A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency, Science Immunology (2023). DOI: 10.1126/sciimmunol.ade7953

Comment by Dr. Krishna Kumari Challa on January 24, 2023 at 9:58am

Head injury is associated with doubled mortality rate long-term

Adults who suffered any head injury during a 30-year study period had two times the rate of mortality than those who did not have any head injury, and mortality rates among those with moderate or severe head injuries were nearly three times higher, according to new research.

Head injury can be attributed to a number of causes, from motor vehicle crashes, unintentional falls, or sports injuries. What's more, head injury has been linked with a number of long-term health conditions, including disability, late-onset epilepsy, dementia, and stroke.

Studies have previously shown increased short-term mortality associated with head injuries primarily among hospitalized patients. This longitudinal study evaluated 30 years of data from over 13,000 community-dwelling participants (those not hospitalized or living in nursing home facilities) to determine if head injury has an impact on mortality rates in adults over the long term. Investigators found that 18.4 percent of the participants reported one or more head injuries during the study period, and of those who suffered a head injury, 12.4 percent were recorded as moderate or severe. The median period of time between a head injury and death was 4.7 years.

Death from all causes was recorded in 64.6 percent of those individuals who suffered a head injury, and in 54.6 percent of those without any head injury. Accounting for participant characteristics, investigators found that the mortality rate from all-causes among participants with a head injury was 2.21 times the mortality rate among those with no head injury. Further, the mortality rate among those with more severe head injuries was 2.87 times the mortality rate among those with no head injury.

Investigators also evaluated the data for specific causes of death among all participants. Overall, the most common causes of death were cancers, cardiovascular disease, and neurologic disorders (which include dementia, epilepsy, and stroke). Among individuals with head injuries, deaths caused by neurologic disorders and unintentional injury or trauma (like falls) occurred more frequently.

When investigators evaluated specific neurologic causes of death among participants with head injury, they found that nearly two-thirds of neurologic causes of death were attributed to neurodegenerative diseases, like Alzheimer's and Parkinson's disease. These diseases composed a greater proportion of overall deaths among individuals with head injury (14.2 percent) versus those without (6.6 percent).

This highlights the importance of safety measures, like wearing helmets and seatbelts, to prevent head injuries.

 Holly Elser et al, Head Injury and Long-term Mortality Risk in Community-Dwelling Adults, JAMA Neurology (2023). DOI: 10.1001/jamaneurol.2022.5024

Comment by Dr. Krishna Kumari Challa on January 24, 2023 at 9:16am

Milky Way found to be too big for its 'cosmological wall'

Is the Milky Way special, or, at least, is it in a special place in the universe? An international team of astronomers has found that the answer to that question is yes, in a way not previously appreciated. A new study shows that the Milky Way is too big for its "cosmological wall," something yet to be seen in other galaxies.

A cosmological wall is a flattened arrangement of galaxies found surrounding other galaxies, characterized by particularly empty regions called "voids" on either side of it. These voids seem to squash the galaxies together into a pancake-like shape to make the flattened arrangement. This wall environment, in this case called the Local Sheet, influences how the Milky Way and nearby galaxies rotate around their axes, in a more organized way than if we were in a random place in the universe, without a wall.

Typically, galaxies tend to be significantly smaller than this so-called wall. The Milky Way is found to be surprisingly massive in comparison to its cosmological wall, a rare cosmic occurrence.

The new findings are based on a state-of-the-art computer simulation, part of the IllustrisTNG project. The team simulated a volume of the universe nearly a billion light-years across that contains millions of galaxies. Only a handful—about a millionth of all the galaxies in the simulation—were as "special" as the Milky Way, i.e., both embedded in a cosmological wall like the Local Sheet, and as massive as our home galaxy.

M A Aragon-Calvo et al, The unusual Milky Way-local sheet system: implications for spin strength and alignment, Monthly Notices of the Royal Astronomical Society: Letters (2022). DOI: 10.1093/mnrasl/slac161

Comment by Dr. Krishna Kumari Challa on January 22, 2023 at 8:57am

Microalgae abundance and proportions affect nutrient exchange in a coral symbiotic relationship

Comment by Dr. Krishna Kumari Challa on January 22, 2023 at 8:54am

Harnessing the healing power within our cells

Researchers have identified a pathway in cells that could be used to reprogram the body’s immune system to fight back against both chronic inflammatory and infectious diseases. Molecular bio-scientists have discovered that a molecule derived from glucose in immune cells can both stop bacteria growing and dampen inflammatory responses.

The effects of this molecule called ribulose-5-phosphate on bacteria are striking – it can cooperate with other immune factors to stop disease-causing strains of the E. coli bacteria from growing.  It also reprograms the immune system to switch off destructive inflammation, which contributes to both life-threatening infectious diseases such as sepsis as well as chronic inflammatory diseases like respiratory diseases, chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, heart disease, stroke, diabetes and dementia.

The research was carried out on a strain of E. coli bacteria that causes approximately 80 per cent of urinary tract infections and is a common cause of sepsis. Pre-clinical trials were used to confirm the role of this pathway in controlling bacterial infections.

 Human cells were also used to demonstrate that ribulose-5-phosphate reduces the production of molecules that drive chronic inflammatory diseases.

Host-directed therapies which train our immune systems to fight infections, will become increasingly important as more types of bacteria become resistant to known antibiotics.

A bonus is that this strategy also switches off destructive inflammation, which gives it the potential to combat chronic disease.

By boosting the immune pathway that generates ribulose-5-phosphate, scientists may be able to give the body the power to fight back against inflammatory and infectious diseases – not one, but two of the major global challenges for human health.

Many current anti-inflammatory therapies target proteins on the outside of cells but because this pathway occurs inside cells, the researchers devised a new approach to target the pathway using mRNA technology.

Kaustav Das Gupta et al, HDAC7 is an immunometabolic switch triaging danger signals for engagement of antimicrobial versus inflammatory responses in macrophages, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2212813120

Comment by Deepak Menon on January 22, 2023 at 7:10am

Very very interesting research on the DNA trap. Will these trap specific viruses and how will they recognise them?

Comment by Dr. Krishna Kumari Challa on January 21, 2023 at 11:10am

How antioxidants produced by mitochondria reach the cell surface to protect against death

Antioxidants are often advertised as a cure-all in nutrition and offered as dietary supplements. However, our body also produces such radical scavengers itself, one of which is coenzyme Q. Now researchers have discovered how the substance, which is produced in our mitochondria, reaches the cell surface and protects our cells from dying.

Coenzyme Q is an antioxidant that is essential for our body. A deficiency of coenzyme Q leads to serious diseases such as Leigh syndrome—a hereditary disease in which certain brain regions become affected and, among other things, muscle weakness  can occur. A deficiency of coenzyme Q is also one of the first signs of aging and can occur as early as the early 20s. But why can't we simply take this substance in with our food?

Because Coenzyme Q is a highly hydrophobic molecule that our bodies absorb very little from food.  But it is also a problem in our cells that coenzyme Q is not water soluble. The antioxidant is formed in mitochondria and must pass through the watery cell interior called cytoplasm to the surface of the cells in order to neutralize oxidized lipid species.

With this new research work, scientists have now been able to identify the proteins involved in coenzyme Q transport from the mitochondria to the cell surface.

The researchers found that an enzyme called STARD7 helps transport the coenzyme. This protein is not only localized in the mitochondria, but also inside the cytoplasm. The mitochondria actively transport coenzyme Q to the cell surface to protect cells from cell death. It is as if the mitochondria deliver band-aids to the surface to protect the cell. This again shows that mitochondria are not only important as an energy supplier for our cells, but also play crucial regulatory roles.

A precise understanding of this transport process will enable Coenzyme Q to be delivered into the cells of affected patients and thus provide a new therapeutic approach for diseases such as Leigh syndrome.

Soni Deshwal et al, Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7, Nature Cell Biology (2023). DOI: 10.1038/s41556-022-01071-y

Comment by Dr. Krishna Kumari Challa on January 21, 2023 at 10:58am

Using origami DNA to trap large viruses and prevent infections

A team of researchers has found that it is possible to build origami DNA structures that can be used to trap large viruses. In their paper published in the journal Cell Reports Physical Science, the group describes how they built their structures and how well they worked when tested.

As the global pandemic continues, albeit in a less deadly phase, the medical science community continues to look for ways to prevent people from becoming infected with not just the SARS-CoV-2 virus, but all viruses. One such approach involves the use of structures designed to attract viruses and when they come close enough, to trap them. In this new effort, the researchers have tested the idea of using origami DNA. DNA origami involves strands of DNA manipulated to create two or three-dimensional shapes, all at the nanoscale. In this new work, the researchers expanded on prior work done by some of the team members who together had developed a process for using DNA origami to trap very small viral particles. To create larger traps for larger viruses, the team used both long and short strands of DNA that had been designed to stick together in useful ways. They then used them to create triangular 2D building blocks that when placed near each other would snap together like puzzle pieces. They then set to work creating structures that they believed could serve as virus traps. After confirming that the structures they had in mind had the desired shapes, they coated the insides of them with chemicals or antibodies that are known to bind with viruses. They then tested the traps by placing them in the vicinity of live viruses. They found that the traps worked as hoped, capturing viruses as large as 100nm in diameter. When trapped, viruses were unable to bond with other cells, thus preventing infections. The researchers tested their traps with several types of viruses—from Zika, to influenza to SARS-CoV-2—and found that they worked equally well on all of them. They also found that they could make them more durable by shining a UV light on them and by covering them with an oligosine polymer. They next plan to test their traps in live lab animals.

Alba Monferrer et al, DNA origami traps for large viruses, Cell Reports Physical Science (2023). DOI: 10.1016/j.xcrp.2022.101237

Comment by Dr. Krishna Kumari Challa on January 21, 2023 at 10:39am

74,963 Kinds of Ice

There are somewhere between 20 and 74,963 kinds of ice. Water can do all kinds of weird stuff when it freezes. So far scientists have experimentally shown crystal structures for 19 kinds of ice. Or maybe 20, depending on who you ask. We’re going to charge through as many as we can in ten minutes or so.

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