Comment

Comment by Dr. Krishna Kumari Challa on November 20, 2021 at 10:28am

This study on UTI was a proof of concept that whole-cell vaccines are more effective in this extreme, lethal-sepsis model. Showing that this works against recurrent UTI would be a significant breakthrough.

Beyond recurrent UTI or urosepsis, researchers think the antigen depot method could be applied broadly to bacterial infections, including endocarditis and tuberculosis.

Michael A. Luzuriaga et al, Metal–Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection, ACS Nano (2021). DOI: 10.1021/acsnano.1c03092

https://phys.org/news/2021-11-scientists-vaccine-method-recurrent-u...

Part 3

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Comment by Dr. Krishna Kumari Challa on November 20, 2021 at 10:27am

Vaccines using whole-cell dead bacteria haven't succeeded because the cells typically don't last long enough in the body to produce long-term, durable immune responses.

That's the reason for  this new MOF antigen depot: It allows an intact, dead pathogen to exist in tissue longer, as if it were an infection, in order to trigger a full-scale immune system response.

The metal-organic framework Gassensmith's team developed encapsulates and immobilizes an individual bacterium cell in a crystalline polymeric matrix that not only kills the bacterium but also preserves and stabilizes the dead cell against high temperature, moisture and organic solvents.

In their experiments, the researchers used a strain of Escherichia coli. There are no vaccines against any pathogenic strain of this bacterium. Uropathogenic E. coli causes about 80% of all community-acquired UTIs.

"When we challenged these mice with a lethal injection of bacteria, after they were vaccinated, almost all of our animals survived, which is a much better performance than with traditional vaccine approaches," Gassensmith said. "This result was repeated multiple times, and we're quite impressed with how reliable it is."

Although the method has not yet been tested in humans, De Nisco said it has the potential to help millions of patients.

part 2

Comment by Dr. Krishna Kumari Challa on November 20, 2021 at 10:08am

Scientists develop promising vaccine method against recurrent UTI

Researchers are investigating the use of whole-cell vaccines to fight urinary tract infection (UTI), part of an effort to tackle the increasingly serious issue of antibiotic-resistant bacteria. They  recently demonstrated the use of metal-organic frameworks (MOFs) to encapsulate and inactivate whole bacterial cells to create a "depot" that allows the vaccines to last longer in the body.

The resulting study, published online Sept. 21 in the American Chemical Society's journal ACS Nano, showed that in mice this method produced substantially enhanced antibody production and significantly higher survival rates compared to standard whole-cell vaccine preparation methods.

Vaccination as a therapeutic route for recurrent UTIs is being explored because antibiotics aren't working anymore. Patients are losing their bladders to save their lives because the bacteria cannot be killed by antibiotics or because of an extreme allergy to antibiotics, which is more common in the older population than people may realize. If not successfully treated, a UTI can lead to sepsis, which can be fatal. Even if you clear the bacteria from the bladder, populations persist elsewhere and usually become resistant to the antibiotic used. When patients accumulate antibiotic resistances, they're eventually going to run out of options.

Vaccines work by introducing a small amount of killed or weakened disease-causing germs, or some of their components, to the body. These antigens prompt the immune system to produce antibodies against a particular disease. Building vaccines against pathogenic bacteria is inherently difficult because bacteria are significantly larger and more complex than viruses. Selecting which biological components to use to create antigens has been a major challenge.

Consequently, using the entire cell is preferable to choosing just a piece of a bacterium

part 1

Comment by Dr. Krishna Kumari Challa on November 20, 2021 at 9:32am

Dengue antibodies can knock out Zika—and vice versa

Cross-protective antibodies from dengue and Zika last far longer than previously thought, scientists have found in a massive study involving more than 4,000 children in Nicaragua.

The 11-year longitudinal analysis unexpectedly revealed that antibodies from either dengue or Zika—which naturally protect against infections caused by either virus—remain stable for years and do not precipitously wane.

Solving scientific mysteries about old foes such as dengue, and an emerging infection like Zika, helps lay the scientific groundwork for better responding to future outbreaks.

It has been previously thought that initial infection with dengue or Zika [viruses] leads to antibodies that are initially protective but wane over time to a point where they become enhancing and drive severe disease.

Cross-reactive antibody protection became abundantly clear during the Zika epidemic of 2015, which swept through multiple Caribbean, Central and South American countries. Stunningly, the incidence of dengue disease dropped dramatically in the midst of the surging Zika outbreak. Dengue and Zika are members of the same family of flaviviruses, so patients who had recovered from dengue infections had cross-protective antibodies capable of neutralizing dengue and Zika. Both viruses are carried by Aedes aegypti mosquitoes.

Yet, previous studies had suggested that the cross-reactive antibodies lasted only two years before dropping to levels that actually made future dengue infections more likely. Scientists in 2015 also had recognized—at least anecdotally—that some people surprisingly had immune protection against the newly emerged Zika virus.

So scientists designed a new study to understand this that allowed them to track antibody responses to initial and secondary dengue as well as to Zika infections. The team focused on community-based and hospital cohorts of children in Nicaragua. To their surprise, instead of diminishing, the antibody kenetics research allowed the scientists to conclude that cross-protective antibodies remained stable for as long as 11 years.

They found that t overall dengue virus iELISA titers stabilized by eight months after primary dengue infection to a half-life longer than a human life and [then] waned.

The half-life, which is longer than a human life, was estimated at 130,000 years, according to the team's research.

The team also observed cross-protective antibodies that were similarly stable in children who were infected with Zika virus. However, the amount of cross-protective antibodies differed across children, which suggests that the quantity of antibodies determines the degree of protection.

Leah C. Katzelnick et al, Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abg9478

https://medicalxpress.com/news/2021-11-secrets-antibodies-dengue-zi...

Comment by Dr. Krishna Kumari Challa on November 20, 2021 at 9:03am

The Birth of Microbiology

Comment by Dr. Krishna Kumari Challa on November 19, 2021 at 3:51pm

Severe spinal cord injuries repaired with 'dancing molecules'

https://www.youtube.com/watch?v=Q_xvCE904YU&t=184s

Comment by Dr. Krishna Kumari Challa on November 19, 2021 at 3:28pm

Warmer soil stores less carbon: study

Global warming will cause the world's soil to release carbon, new research shows.

Scientists used data on more than 9,000 soil samples from around the world, and found that carbon storage "declines strongly" as average temperatures increase.

This is an example of a "positive feedback", where global warming causes more carbon to be released into the atmosphere, further accelerating climate change.

Importantly, the amount of carbon that could be released depends on the soil type, with coarse-textured (low-clay) soils losing three times as much carbon as fine-textured (clay-rich) soils.

The researchers  say their findings help to identify vulnerable carbon stocks and provide an opportunity to improve Earth System Models (ESMs) that simulate future climate change.

Because there is more carbon stored in soils than there is in the atmosphere and all the trees on the planet combined, releasing even a small percentage could have a significant impact on our climate.

This analysis identified the carbon stores in coarse-textured soils at high-latitudes (far from the Equator) as likely to be the most vulnerable to climate change.

Such stores, therefore, may require particular attention given the high rates of warming taking place in cooler regions.

In contrast, researchers found carbon stores in fine-textured soils in tropical areas to be less vulnerable to climate warming.

By comparing carbon storage in places with different average temperatures, the researchers estimated the likely impact of global warming.

For every 10°C of increase in temperature, average carbon storage (across all soils) fell by more than 25%.

These results make it clear that, as temperatures rise, more and more carbon is release from soil.

The differences in carbon storage based on soil texture occur because finer soils provide more mineral surface area for carbon-based organic material to bond to, reducing the ability of microbes to access and decompose it.

Temperature effects on carbon storage are controlled by soil stabilisation capacities, Nature Communications (2021). DOI: 10.1038/s41467-021-27101-1

https://phys.org/news/2021-11-warmer-soil-carbon.html?utm_source=nw...

Comment by Dr. Krishna Kumari Challa on November 19, 2021 at 11:19am

Cancer cells use 'tiny tentacles' to suppress the immune system

To grow and spread, cancer cells must evade the immune system. Investigators from Brigham and Women's Hospital and MIT used the power of nanotechnology to discover a new way that cancer can disarm its would-be cellular attackers by extending out nanoscale tentacles that can reach into an immune cell and pull out its powerpack. Slurping out the immune cell's mitochondria powers up the cancer cell and depletes the immune cell. The new findings, published in Nature Nanotechnology, could lead to new targets for developing the next generation of immunotherapy against cancer.

Cancer kills when the immune system is suppressed and cancer cells are able to metastasize, and it appears that nanotubes can help them do both. This is a completely new mechanism by which cancer cells evade the immune system and it gives us a new target to go after.

To investigate how cancer cells and immune cells interact at the nanoscale level, researchers set up experiments in which they co-cultured breast cancer cells and immune cells, such as T cells. Using field-emission scanning electron microscopy, they caught a glimpse of something unusual: Cancer cells and immune cells appeared to be physically connected by tiny tendrils, with widths mostly in the 100-1000 nanometer range. (For comparison, a human hair is approximately 80,000 to 100,000 nanometers). In some cases, the nanotubes came together to form thicker tubes. The team then stained mitochondria—which provide energy for cells—from the T cells with a fluorescent dye and watched as bright green mitochondria were pulled out of the immune cells, through the nanotubes, and into the cancer cells.

By carefully preserving the cell culture condition and observing intracellular structures, researchers saw these delicate nanotubes and they were stealing the immune cells' energy source. It was very exciting because this kind of behavior had never been observed before in cancer cells. The researchers then looked to see what would happen if they prevented the cancer cells from hijacking mitochondria. When they injected an inhibitor of nanotube formation into mouse models used for studying lung cancer and breast cancer, they saw a significant reduction in tumor growth.

Hae Jang, Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells, Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-01000-4. www.nature.com/articles/s41565-021-01000-4

https://phys.org/news/2021-11-cancer-cells-tiny-tentacles-suppress....

Comment by Dr. Krishna Kumari Challa on November 19, 2021 at 9:16am

the results also show a clear inverse relationship between the level of antigenic diversity in a given year and epidemic levels. When Thailand experienced large epidemic outbreaks, antigenic diversity was low. But in years when epidemic levels were lower than average, the antigenic diversity was higher.

"In general, it's been thought that if you get infected with one serotype of DENV then you are immune to that serotype for the rest of your life. But there have been observations where that seems to not be strictly true."

One explanation for re-infections is that dengue viruses may be subject to natural selective forces to evade the immune system of previously infected individuals. In essence, they must change just enough to avoid immune detection in a host where another serotype has already caused an infection.

These findings suggest that the dengue viruses are moving away from the viruses that generated immunity in the population in the past. It's sort of like the flu story, dengue is evolving to escape the immunity that is in the population at any particular time. But it seems to be happening at a slower pace with dengue than influenza.

Researchers already knew that there is a complex interplay between immunity and the dengue virus. When someone is exposed to a serotype of this virus, they will typically experience a mild infection that results in partial infection. But when they are exposed again, the partial immunity can trigger an overreaction that can lead to serious outcomes. The dengue virus appears, in these cases, to not only evade the immune response, but use it to its advantage to potentially increase its rate of growth.

Ninety to 95% of the people showing up at a hospital in Bangkok with dengue are having their second infection. "And most people who live their whole lives in Bangkok are getting infected multiple times."

This enhanced infection phenomenon may also contribute to the evolution of the pathogen, selecting for viruses that are similar enough to take advantage of the Immune response.

Overall, viruses were growing more different from each other over time, but scientists also observed that they grew closer together during some periods of time, particularly early in the time series. This indicates a tradeoff between evading immunity and taking advantage of partial immunity.

This paper is suggesting that the dengue viruses are changing and we need to update how we do surveillance to better understand immunity in populations and to ultimately reduce the number of people who get sick.

Leah Katzelnick et al, Antigenic evolution of dengue viruses over 20 years, Science (2021). DOI: 10.1126/science.abk0058. www.science.org/doi/10.1126/science.abk0058

https://phys.org/news/2021-11-host-immunity-viral-evolution-dengue....

Part 3

Comment by Dr. Krishna Kumari Challa on November 19, 2021 at 9:11am

The new study used 1,944 archival blood samples from Bangkok. The samples were preserved from people known to be ill with dengue and they represent all four dengue virus strains from every year between 1994 and 2014. The team genetically sequenced more than 2,000 virus samples.

The researchers then performed tests on a smaller subset of samples that represented a time series of each strain. From this, they then characterized the antigenic relationship of the strains to each other through time. Antigenic relationships characterize how well an immune response to one virus protects against other viruses.

Researchers  found that there is a pattern like influenza, where you get different viruses every year that are driven by natural selection for viruses that evade the human immune response to the population.  This work shown that that this is also happening with dengue.

The team used a process called antigenic cartography which makes a map to visualize the relatedness of viruses.

"When two viruses are close on that map, then that means immune responses 'sees' the viruses as similar," Katzelnick says. "For example, if you are infected with one virus, then an immune response to that virus would protect you against another virus that is nearby on the map."

The team found an overall pattern of dengue virus strains evolving away from each other over the 20-year study timeframe. While the serotypes at times oscillated closer, in general they grew further apart.

Part 2

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