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Creation of new brain cells plays underappreciated role in Alzheimer’s

Creation of new brain cells plays underappreciated role in Alzheimer’s

Much of the research on the underlying causes of Alzheimer’s disease focuses on amyloid beta (Aß), a protein that accumulates in the brain as the disease progresses. Excess Aß proteins form clumps or “plaques” that disrupt communication between brain cells and trigger inflammation, eventually leading to widespread loss of neurons and brain tissue.

Aß plaques will continue to be a major focus for Alzheimer’s researchers. However, innovative research by neuroscientists at the University of Chicago looks at another process that plays an underappreciated role in the progression of the disease.

In a new study published in the Journal of Neuroscience, Prof. Sangram Sisodia, a leading expert on the biology of Alzheimer’s disease, and his colleagues show how in genetic forms of Alzheimer’s, a process called neurogenesis—the creation of new brain cells—can be disrupted by the brain’s own immune cells.

Some types of early onset, hereditary Alzheimer’s are caused by mutations in two genes called presenilin 1 (PS1) and presenilin 2 (PS2). Previous research has shown that when healthy mice are placed into an “enriched” environment where they can exercise, play and interact, they have a huge increase in new brain cells being created in the hippocampus—the part of the brain that is important for memory. But when mice carrying mutations to PS1 and PS2 are placed in an enriched environment, they don’t show the same increase in new brain cells. They also start to show signs of anxiety, a symptom often reported by people with early onset Alzheimer’s.

This led Sisodia to think that something besides genetics had a role to play. He suspected that the process of neurogenesis in mice both with and without Alzheimer’s mutations also could be influenced by other cells that interact with the newly forming brain cells.

The researchers focused on microglia, a kind of immune cell in the brain that usually repairs synapses, destroys dying cells and clears out excess Aß proteins. When the researchers gave the mice a drug that causes microglial cells to die, neurogenesis returned to normal. The mice with presenilin mutations were then placed into an enriched environment and they were fine; they didn’t show any memory deficits or signs of anxiety, and they were creating the normal, expected number of new neurons.

“It’s the most astounding result to me,” said Sisodia, the Thomas Reynolds Sr. Family Professor of Neurosciences at UChicago. “Once you wipe out the microglia, all these deficits that you see in these mice with the mutations are completely restored. You get rid of one cell type, and everything is back to normal.”

“It’s the most astounding result to me … You get rid of one cell type, and everything is back to normal.”

—Prof. Sangram Sisodia

Sisodia thinks the microglia could be overplaying their immune system role in this case. Alzheimer’s disease normally causes inflammation in the microglia, so when they encounter newly formed brain cells with presenilin mutations they may overreact and kill them off prematurely. He feels that this discovery about the microglia’s role opens another important avenue toward understanding the biology of Alzheimer’s disease.

“I’ve been studying amyloid for 30 years, but there’s something else going on here, and the role of neurogenesis is really underappreciated,” he said. “This is another way to understand the biology of these genes that we know significantly affect the progression of disease and loss of memory.”

Additional authors include Sylvia Ortega-Martinez, Nisha Palla, Xiaoqiong Zhang and Erin Lipman from the University of Chicago.

Citation: “Deficits in Enrichment-Dependent Neurogenesis and Enhanced Anxiety Behaviors Mediated by Expression of Alzheimer’s Disease-Linked Ps1 Variants Are Rescued by Microglial Depletion.” Journal of Neuroscience, Aug. 21, 2019. DOI: 10.1523/JNEUROSCI.0884-19.2019

Materials provided by the University of Chicago

Scientists Have Developed a Genius Method That Actually Regenerates Tooth Enamel

Researchers come up with a technique which regenerates tooth enamel

  • A properly designed material which is made of calcium phosphate ion clusters can be used to create a precursor layer for inducing the epitaxial crystal growth of enamel apatite.
  • This needed a new type of calcium phosphate ion clusters which had a diametrical measurement of 1.5 nanometres. They were stabilised in ethanol with the help of triethylamine

Tooth enamel is the hardest substance in our body. It is irreplaceable and many people all over the world suffer from tooth decay due to loss of enamel. However new studies offer hope to end this problem. 

Researchers in China have come up with a liquid solution which can help in growing back the outer surface of the damaged tooth enamel with the help of a material which mimics the mineralisation process of the protective outer layer of our teeth. The work appears in Science Advances journal

Tooth enamel is created in a biomineralisation process where cells known as ameloblasts generate proteins which harden to form the tough outer coating of our teeth. But ameloblasts are only present during the course of tooth development as a result of which the mature teeth cannot repair itself after its formation. 

Researchers have tried several approaches to coax enamel remineralisation artificially but they have mostly failed since the crystalline structure of the enamel has not been properly replicated in the laboratory. Zhaoming Liu, biomimetics and materials researcher said that in this new technique they reveal that a properly designed material which is made of calcium phosphate ion clusters can be used to create a precursor layer for inducing the epitaxial crystal growth of enamel apatite. This mimics the biomineralisation crystalline-amorphous frontier for the development of hard tissue. 

This needed a new type of calcium phosphate ion clusters which had a diametrical measurement of 1.5 nanometres. They were stabilised in ethanol with the help of triethylamine which avoided them being clumped together. They were then applied to the human teeth which were donated by the patients. The super-small clusters properly fused to form the fish scale-like structure of native enamel. This replicated the tooth coating with an equally hard layer which had a thickness of 2.8 micrometres in 48 hours. 

That is very much thinner compared to the full layer of normal tooth enamel, however, researchers feel that repeated coatings of CPIC solution could increase the thickness along with further refinements. Liu said that that generated enamel has the similar structure and properties to that of native enamel. Researchers hope to generate tooth enamel without fillings that contain entirely different materials. They are expecting to begin trials within one to two years. 

To meet the deadline, scientists have to prove that the material is safe as presently there are concerns regarding the toxicity of triethylamine, which is the stabilising compound. It evaporates during the process hence should not be of any risk. The substance is currently being tested in mice. It might take some time before it is adopted for daily use and till then the conventional advice on dental health has to be followed. Chen Haifeng, Peking University who was not part of the study thinks artificial replacement can never properly replicate the natural teeth. 

Journal Reference: Science Advances journal

Why we’re so emotionally invested in the semicolon

Why we’re so emotionally invested in the semicolon

“The semicolon is a place where our anxieties and our aspirations about language, class and education are concentrated so that in this small mark big ideas are distilled down to a few winking drops of ink,” writes Cecelia Watson, AM’05, PhD’11.

Cecelia Watson

Cecelia Watson, AM’05, PhD’11

That’s a lot of baggage for a half-comma, half-colon, but Watson shows it’s more than up to the task in Semicolon: The Past, Present and Future of a Misunderstood Mark (Ecco, 2019)—a book that already has garnered the Bard College scholar critical acclaim from The New YorkerThe New York Times and National Public Radio.

Tracing the hybrid mark from its origins among 15th-century Italian humanists, her story describes early attempts to “scientize” language through grammar rules and raises questions about who made—and didn’t make—those rules. And with examples drawn from literature, legal history and her own life as a “reformed grammar fetishist,” Watson seeks to persuade readers to learn to love the semicolon. The following Q&A with The University of Chicago Magazine have been edited and condensed.

Why a book on the semicolon?

What really surprised me when I was working on this as an academic topic was the emotional investment people had in the semicolon. Usually when you’re giving an academic talk, everybody does the super professional, very objective, I’m-detached-from-this-topic type of performance. But when I would talk about the semicolon, people would tell me all of these personal stories, even about falling in love because of conversations about the semicolon—not the usual thing you hear when you’re an academic. That clued me in that maybe there was a way to reach out to a broader audience. When we pitched it to publishers, I think we ended up with seven houses in the auction.

Why do some people have such strong negative feelings about this punctuation mark?

Distaste for the semicolon comes from a lot of different angles. Some people have a sheer aesthetic distrust of it. They just like short sentences, for instance. They think that’s more direct or more pleasing in some way, or more clear. The semicolon, of course, can facilitate very long sentences. Other people think it’s elitist, and a reader is going to roll their eyes or feel alienated, and in some ways belittled, by the author’s advertisement of his or her own education level. Others have bad childhood memories associated with trying to use the semicolon and failing and being embarrassed.

Is there a way we could be using semicolons that we aren’t currently?

One use that has fallen out of practice is using the semicolon as a colon or sometimes a comma. You see this a lot in the late 19th or early 20th century. Nobody liked the colon at the time, and everybody loved the semicolon, so they wanted to stick it wherever they could. I think less about particular styles of semicolon usage and more about how easy it is to be lazy and use catch-all punctuation marks. I’ll just put dashes and ellipses for everything. Those are all points at which we could say, “Would a semicolon actually provide some interest here? Would it help create some new rhythms on the page? Would it make anything a little easier to read?”

Your book ranges into broader questions about who gets to dictate the rules of language. How did that happen?

Initially I was focused on where rules come from. A lot of the people who influenced me when I was at UChicago taught me to see that even things we wouldn’t think of as having a history have a history, like a set of punctuation rules. My discipline, history and philosophy of science, had a huge role in the history of the semicolon. A lot of the history of grammar rules is a direct function of this mid- to late-1800s obsession with being scientific and objective. Grammar was not excepted from that.

One thing that I hope the book’s readers notice is that every single person in the section about the founding of grammar is an elite white male. That’s no accident. It’s also no accident that when grammar rules were invented, women, and to some extent people of color and poor people, were gaining unprecedented access to education. Grammar is, and has always been, an incredibly effective way to enforce the status quo.

Materials provided by the University of Chicago

Researchers have finally created a quantum X-Ray device

Researchers have finally created a quantum X-Ray device

A research team has demonstrated quantum enhancement in a real X-ray machine, thereby achieving the goal of elimination of background noise for precision detection. The relationship between photon pairs on quantum scales can be used to generate sharp, high-resolution images compared to classical optics. This field is called quantum imaging and has huge potential since optical light can be used to show objects that cannot be seen normally like bones and organs. Quantum correlation describes several relationships between photon pairs, among which entanglement is one and it is used in optical quantum imaging.

The technical challenges of generating entangled photons in X-ray wavelength are greater than optical light, so the team used a different approach. They used a method called quantum illumination to minimize background noise. Using parametric down-conversion (PDC), the researchers split a high energy photon into two low energy photons, signal photon, and idler photon. Researchers mentioned that the application of X-Ray PDC as a source of ghost imaging has been demonstrated recently.  In previous publications, the photon statistics were not measured with any experimental evidence to date, which is generated by X-Ray PDC. Similarly, the observations of quantum enhancement sensitivity were not reported at X-ray wavelengths. The work appears in Physical Review X.

The X-Ray PDC was achieved with the help of a diamond crystal. The non-linear structure of crystal splits X-Ray photons into signal and idler beams, each having half the energy of the pump beam. The team scaled up power by using SPring-8 synchrotron in Japan. They shot a 22 KeV beam of X-rays at their crystal, splitting into two beams, carrying the energy of 11 KeV. The signal beam is sent towards the object which has to be imaged. Here, it is a small metal piece with three slits and a detector on the other side. The idler beam is directly sent to another detector so that each beam hits its respective detector at the same place and time.

The researchers then compared the detections. They found 100 correlated photons per point in the image and 10,000 background photons. Researchers could match each idler to the signal and could trace back the photons which came from the beam, thereby eliminating the noise. They later compared the images to the images developed using non-correlated photons. The correlated photons produced a sharper image.

Quantum X-ray imaging could have many uses outside current X-ray technology with a benefit of lower X-ray radiation required for imaging. This means that samples which are easily damaged by X-Rays could be imaged along with the samples with lower temperature requirement. As quantum X-Ray requires particle accelerator, there are no medical applications currently. The researchers say that they have demonstrated the ability to utilize the strong time-energy correlations of photon pairs for quantum-enhanced photodetection. The procedure they have presented possesses great potential for improving the performances of X-ray measurements.

Journal Reference: Physical Review X.

A comprehensive catalogue of human digestive tract bacteria

A comprehensive catalogue of human digestive tract bacteria

The human digestive tract is home to thousands of different strains of bacteria. Many of these are beneficial, while others contribute to health problems such as inflammatory bowel disease. Researchers from MIT and the Broad Institute have now isolated and preserved samples of nearly 8,000 of these strains, while also clarifying their genetic and metabolic context.

This data set (BIO-ML), which is available to other researchers who want to use it, should help to shed light on the dynamics of microbial populations in the human gut and may help scientists develop new treatments for a variety of diseases, says Eric Alm, director of MIT’s Center for Microbiome Informatics and Therapeutics and a professor of biological engineering and of civil and environmental engineering at MIT.

“There’s a lot of excitement in the microbiome field because there are associations between these bacteria and health and disease. But we’re lacking in being able to understand why that is, what’s the mechanism, and what are the functions of those bacteria that are causing them to associate with disease,” says Alm, who is the senior author of the study.

The researchers collected stool samples from about 90 people, for up to two years, allowing them to gain insight into how microbial populations change over time within individuals. This study focused on people living in the Boston area, but the research team is now gathering a larger diversity of samples from around the globe, in hopes of preserving microbial strains not found in people living in industrialized societies.

“More than ever before, modern techniques allow us to isolate previously uncultured human gut bacteria. Exploring this genetic and functional diversity is fascinating — everywhere we look, we discover new things. I’m convinced that enriching biobanks with a large diversity of strains from individuals living diverse lifestyles is essential for future advancements in human microbiome research,” says Mathilde Poyet, a senior postdoc at MIT and one of the lead authors of the study.

MIT research associate Mathieu Groussin and former postdoc Sean Gibbons are also lead authors of the study, which appears in the Sept. 2 issue of Nature Medicine. Ramnik Xavier, a professor of medicine at Harvard Medical School and member of the Broad Institute, is a senior author of the study along with Alm.

Microbiome dynamics

Humans have trillions of bacterial cells in their digestive tracts, and while scientists believe that these populations change and evolve over time, there has been little opportunity to observe this. Through the OpenBiome organization, which collects stool samples for research and therapeutic purposes, Alm and his colleagues at MIT and the Broad Institute had access to fecal samples from about 90 people.

For most of their analysis, the researchers focused on microbes found in about a dozen individuals who had provided samples over an extended period, up to two years.

“That was a unique opportunity, and we thought that would be a great set of individuals to really try to dig down and characterize the microbial populations more thoroughly,” Alm says. “To date there hadn’t been a ton of longitudinal studies, and we wanted to make that a key focus of our study, so we could understand what the variation is day-to-day.”

The researchers were able to isolate a total of 7,758 strains from the six major phyla of bacteria that dominate the human GI tract. For 3,632 of these strains, the researchers sequenced their full genomes, and they also sequenced partial genomes of the remaining strains.

Analyzing how microbial populations changed over time within single hosts allowed the researchers to discover some novel interactions between strains. In one case, the researchers found three related strains of Bacteroides vulgatus coexisting within a host, all of which appeared to have diverged from one ancestor strain within the host. In another case, one strain of Turicibacter sanguinis completely replaced a related strain of the same species nearly overnight.

“This is the first time we’re getting a glimpse of these really different dynamics,” Alm says.

Population variation

The researchers also measured the quantities of many metabolites found in the stool samples. This analysis revealed that variations in amino acid levels were closely linked with changes in microbial populations over time within a single person. However, differences between the composition of microbial populations in different people were more closely associated with varying levels of bile acids, which help with digestion.

The researchers don’t know exactly what produces these differences in amino acid and bile acid levels, but say they could be influenced by diet — a connection that they hope to investigate in future studies. They have also made all of their data available online and are offering samples of the strains of bacteria they isolated, allowing other scientists to study the functions of these strains and their potential roles in human health.

“Comprehensive and high-resolution collections of bacterial isolates open the possibility to mechanistically investigate how our lifestyle shapes our gut microbiome, metabolism, and inflammation. We aim to provide such a resource to the research community worldwide, including to lower-income research institutions,” Groussin says.

The researchers have also begun a larger-scale project to collect microbiome samples from a greater diversity of populations around the world. They are especially focusing on underrepresented populations who live in nonindustrialized societies, as their diet and microbiomes are expected to be very different from those of people living in industrialized societies.

“It may be that as populations that have been living traditional lifestyles start to switch to a more industrialized lifestyle, they may lose a lot of that biodiversity. So one of the main things we want to do is conserve it, and then later we can go back and characterize it as well,” Alm says.

Materials provided by Massachusetts Institute of Technology

Researchers find explanations behind the mystery of North Pacific gyre

Researchers find explanations behind the mystery of North Pacific gyre

The center of oceans of the Earth are covered with an enormous arrangement of rotating currents known as subtropical gyres, which occupy 40% of the Earth’s surface. They have been considered as stable biological deserts with little deviation in chemical composition or the nutrients needed to sustain life.

The region in the North Pacific Subtropical Gyre ecosystem that occupies the Pacific Ocean between China and the United States has confused scientists over the years by its strange abnormality in chemistry that changes periodically. There is a remarkable variation in the levels of phosphorus and iron which affects the entire nutrient composition and eventually biological productivity.

The research team has found out the explanation behind the variations in the North Pacific Subtropical Gyre ecosystem. It includes Matthew Church, a microbial ecologist with the University of Montana’s Flathead Lake Biological Station, Ricardo Letelier from Oregon State University and David Karl from the University of Hawaii. The work appears in the Proceedings of the National Academy of Sciences.

Church said that the variations in the ocean climate arise to basically control ocean nutrient concentrations by regulating iron supply and altering the kinds of plankton growing in these waters. He also said that after constant, long-term observations on the role of plankton in controlling ocean nutrient availability, their team has finally confirmed that tightly linked plankton supplies nutrients, particularly iron, delivered from the atmosphere.

With the help of three decades of observational data from Station ALOHA, a six-mile area in the Pacific Ocean, the researchers discovered that the periodic shift in the level of iron is due to iron input from Asian dust, accounting for the chemical variances and varying amounts of nutrients to sustain life.

The ocean-atmosphere relationship known as The Pacific Decadal Oscillation varies between weak and strong stages of atmospheric pressure in the northeast Pacific Ocean which is the major factor of the variance. The winds from Asia become stronger and move in a more southern direction in years when the low pressure weakens in the northeast Pacific bringing more dust from Asia and fertilizing the ocean around ALOHA. The opposite occurs when the pressure strengthens.

Phosphorous and iron are the essential components of life and the supply of nutrients is a fundamental controller of ocean productivity. The process of fertilizing the ocean’s upper water level by mixing nutrient-rich water from the bottom is challenging in the North Pacific Subtropical Gyre ecosystem because the waters are very layered and very less mixing takes place. The creatures are allowed to grow and use phosphorus in the upper layers of the ocean when strong Asian winds bring in substantial quantity of iron while they are forced to return to a bottom-water-mixing nutrient delivery system when the Asian winds weaken and iron quantity is reduced creating the periodic ebb and flow of iron and phosphorus levels in the North Pacific Gyre.

Church said that the results from the study highlight the crucial need to include both atmospheric and ocean circulation variability for forecasting the climate change impact on ocean ecosystems. He also added that it confirms the necessity to think about the biology of tightly connected plankton to changes in climate as well as land use which can directly impact dust supply to the ocean.

Researchers hope to see long-term changes in wind patterns across the North Pacific as Earth’s temperature continues to increase. The sources and quantity of iron and other nutrients carried by the wind across the ocean will get affected by the evolution of land use and pollution caused by human activity in Asia.

To know the impact of the changes on ecosystems around the ocean region as well as others around the world, more research is needed.

Journal Reference: Proceedings of the National Academy of Sciences.

Researchers observe human like brain waves in lab grown mini brains

Researchers observe human-like brain waves in lab-grown mini-brains

One method by which researchers can non-invasively analyze the human brain is by developing pea-sized clusters of brain cells called “mini-brains” in the research lab. This week, the team announced that they found human-like brainwaves from these organoids in a magnificent advancement of this field of research.

The movement and nerve tract development of mini-brains has been shown by the previous studies. Biologist Alysson Muotri along with the researchers at the University of California San Diego are the first to study and record human-like neural activity. The researchers wrote that they observed brain wave patterns similar to those of a developing human in their paper published in Cell Stem Cell. Muotri said that sophistication in the in vitro model is a step to help researchers to use mini-brains to study brain development, model diseases, and study about the evolution of the brain. Researchers are good at studying cancer and the heart but the brain has been behind the curve.

Researchers introduced pluripotent human stem cells to a nutrient-rich petri-dish intended to imitate the environment in which our own brains develop to create the technical “mini-brains” called organoids. These cells could be stimulated into building a 3D structure similar to the much smaller human brain because of the multipotential (potential to become any number of different cells) nature of the stem cells. The researchers started to observe the peak of neural activity from the network at around two months of development.

Co-author and Ph.D. student Richard Gao stated that at the beginning, they weren’t checking for parallels between their model and human infant when they began to observe these intermittent bursts of electrical activity. Gao said that they observed a notable feature in organoid oscillations that the network is inactive most of the time and explode spontaneously in every 10-20 seconds. This also occurs in preterm infants called trace discontinu where strong oscillatory transients emphasize the infant’s inactive ECG. He also said that we are very lucky to find a dataset reporting these features in the preterm infant EEG at a point where oscillations vary.

Muotri said that a machine learning algorithm has been prepared by the team to identify important features in the preterm infant EEGs and had it evaluate the cerebral organoids for similarities. It was able to calculate how many weeks the organoids had developed in the culture and could no more distinguish between the organoids and the infant EEGs between 25 and 40 weeks of the organoid’s development.

Muotri and the team clarified that the comparison between the two is not necessarily one-to-one and preterm infant EEGs have some limitations including the impact the thickness of a developing human skull has on readings which differ from the lab-produced organoids.

Arnold Kriegstein, a neurologist from the University of California, San Francisco, who did not contribute to the new study, said that it is difficult to state similarity between organoid activity and preterm EEG. The researchers have clearly shown the development of spontaneous activity in organoids to be reliable on the neuronal activity but organoids are very different from the actual developing cortex and we still need better evidence that the underlying mechanisms are the same even if the phenomenology is similar.

Muotri said that he can’t be sure whether the organoids were developed enough to be considered conscious and questions related to ethical dilemmas might be raised in the future. He intends to hold a meeting at UC San Diego with scientists, philosophers, and ethicists to talk about the ethical future of such technologies. He said that his tendency is always to say that technologies like blood transfusions or organ transplants, or even cars can be used for good as well as bad so brain organoids might also point in a similar direction in the future.

Journal Reference: Cell Stem Cell

A new drug could revolutionize the treatment of neurological disorders

A new drug could revolutionize the treatment of neurological disorders

The international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc. has found a potential drug that may prevent neuronal death through glucose metabolism modification in stressed neurons. The positive results obtained in mice are rather promising for future use in humans. The new drug can be advantageous in neurological conditions ranging from Amyotrophic lateral sclerosis, Alzheimer’s, and Huntington’s diseases to traumatic brain injury and ischemic stroke. The results have been published in the Scientific Reports Journal.

Brain injuries of different nature and neurological disorders are among the most important causes of death worldwide. According to WHO, stroke is the second most common cause of mortality, and more than a third of people who have survived a stroke will have a severe disability.

What is more, as the population ages, millions of more people are posed to develop Alzheimer’s or Parkinson’s diseases in the near future. However, there are no efficient drugs for major neurodegenerative diseases. It is thus critically important to understand the biology of these diseases and to identify new drugs capable of improving quality of life, survival, and,  in the best-case scenario, curing the disease completely.

Glycolysis is generally considered as the metabolic pathway essential for cell survival since it meets cell energy needs in case of intensive energy consumption. However, it is already known that in the brain tissue, the situation is quite different – different cell types show distinct glucose metabolism patterns.  In neurons, only a small portion of glucose is consumed via the glycolysis pathway. At the same time, astrocytes provide nutrients to neurons and utilize glycolysis to metabolize glucose. These differences are mostly due to the special protein called PFKFB3, which is normally absent in neurons and is active in astrocytes. In the case of certain neurological diseases, stroke being one of them, the amount of active PFKFB3 increases in neurons, which is highly stressful for these cells and leads to cell death.

An international team of researchers led by Peter Fedichev, a scientist and biotech entrepreneur from Gero Discovery, and professor Juan P. Bolaños from the University of Salamanca, suggested and further confirmed in the in vivo experiments that a small molecule, the inhibitor of PFKFB3, may prevent cell death in the case of ischemia injury. Inhibition of PFKFB3 improves motor coordination of mice after stroke and reduced brain infarct volume. Moreover, in the experiments using mouse cell cultures, it was shown that PFKFB3 inhibitor protects neurons from the amyloid-beta peptide, the main component of the amyloid plaques found in the brains of Alzheimer’s disease patients.

Professor Juan P. Bolaños: “Excitotoxicity is a hallmark of various neurological diseases, stroke being one of them. Our group has previously established a link between this pathological condition and high activity of PFKFB3 enzyme in neurons, which leads to severe oxidative stress and neuronal death“

“We are glad that our hypothesis that pharmacological inhibition of  PFKFB3 can be beneficial in an excitotoxicity-related condition, such as stroke was confirmed. I would like to note that In our work, we used a known molecule to demonstrate that PFKFB3 blockage has a therapeutic effect. But, we have also performed the same experiments with other proprietary small molecule designed in our company and showed that it had a similar effect. There is, of course, still much work to do. We are currently investigating the efficacy of our compounds in the models of orphan excitotoxicity-related neurological diseases. We have already obtained good safety results in mice and believe that we will be successful in our future investigations” said Olga Burmistrova, Director of preclinical development in Gero Discovery.

Gero Discovery team is planning to proceed with preclinical trials and to move into clinical trials soon. “These promising results bring hope to dozens of millions of patients suffering from life-threatening neurological diseases and provide tremendous business opportunities in many indications with unmet needs. We start communicating with potential investors and co-development partners and invite interested parties to collaborate on the further development of this breakthrough medicine through the preclinical and early clinical stage” mentioned Maksim Kholin, the Gero Discovery Co-Founder and Business Development Director.

Journal Reference: Scientific Reports Journal

Northern White Rhinoceros Angalifu

Scientists fertilise 7 eggs of northern white rhino in an effort to save the species

As Silvia Colleoni injected liquid into a micropipette for inserting the frozen sperm which had been removed from one of the last remaining male northern white rhinos, her hand trembled. She explained the cause of being emotional as it is a manual task and her work could determine if the species would continue to live or get extinct. The artificial fertilization of eggs from the last two remaining females was performed in the Avantea Laboratory in North Italy. The fertilisation process could result in the creation of seven embryos. 

The entire procedure was filmed by the Associated Press who had exclusive access to the laboratory. Eggs were separated from the last remaining female northern white rhinos, Fatu and Najin. Then they were fertilised from the frozen sperms separated from males who were already dead. After 10 days, the result will be out if embryos were formed from the eggs or not. Experts are hoping for the reproduction to be carried through surrogacy as neither of the two females can get pregnant now. 

The process is very strenuous and involves a lot of concentration as joysticks are used to guide the process of fertilisation. For increasing the chances of success, an electronic impulse is also sent. Cesare Galli, founder of Avantea said that they expect for the formation of embryos from some of them as the ultimate goal is to produce a minimum of five animals who would be returned to their natural habitat in Africa. But achieving this could take several decades. 

Avantea reported that only seven from ten eggs which were extracted from the females in Kenya were fit for the process of artificial insemination. The sperm was extracted from northern white bulls, Suni and Saut who lived in a Czech Republic zoo. They are now dead. Their sperm was used to increase the chances of success, as Suni is the half-sibling of Najin. However, it was difficult to work with Saut’s sperm. Galli stated that for greater chances to facilitate the continuation of a species it is better not to wait till the last two individuals of a species are remaining. The last living male rhino was 45-year-old Sudan who was listed in the dating app Tinder and mentioned the “Most Eligible Bachelor” in an attempt to raise funds. However, he was later euthanized for age-related complications. 

His sperm is still in Kenya, as in the future if it is possible to create more embryos then his sperm could be transferred. Northern white rhinos have decreased in population due to excessive poaching for several decades. Other types such as southern white rhino and black rhino are also targeted for their horns which are sold illegally in Asian markets. 

Leibniz Institute for Zoo and Wildlife Research situated in Germany, Avantea, Dvur Kralove Zoo in Czech Republic are some of the organisations trying to save the northern white rhino species. 

anatomy of brain

Researchers figure out why we remember some incidents for a long time and forget some

It often happens that we can remember something which occurred long back but forget the incident that took place recently. Some memories remain stable while others fade away in minutes.

Researchers from Caltech have found that the memories which remain stable over time are encoded by a group of neurons firing in synchrony thus providing redundancy. The work also tries to understand the effects on memory after tragic events such as brain damage or Alzheimer’s disease.

The experiments were carried out in the laboratory of Carlos Lois, a biology professor and affiliated faculty member of Tianqiao and Chrissy Chen Institute for Neuroscience. It appears in the Science journal.

The team was led by Walter Gonzalez, a postdoc scholar. A test was developed for testing the neural activity of mice when they learn and remember a new place. The mouse was kept in a straight enclosure of length 5 feet. Different symbols were marked in different locations on the walls such as a bold plus sign at the rightmost end and angled slash close to the center. Sugar water was placed at the track ends. As the mouse explored places, the activities of certain neurons in the hippocampus were tracked by the scientists.

When initially placed in the track, the mouse wandered till it found the sugar water. Single neurons were activated when it spotted a symbol on the wall. However, on staying longer, the mouse remembered the sugar locations. As the familiarity increased more neurons got activated in synchrony as it spotted the symbols.

To understand the fading of memories, the mice were kept away from the track for 20 days. On getting back to the track, the mice which had strong memories encoded by high numbers of neurons remembered the task easily. So when large groups of neurons encode an activity, the memories can be easily recalled even if some showed different activity or remained silent.

This can be explained in a way similar to how a long story is remembered. For remembering a long story, it can be told to many different people and when all of them gather each can fill in the gaps which the other member has forgotten. By repeating this every time, the story can be preserved with the strengthening of the memory. In a similar way, neurons help each other in encoding memories which stay over time.

Impairment of memory in any form can affect us a lot since our life is basically driven by memories. Senior citizens get affected by this as a part of the aging process. Alzheimer’s disease also has devastating effects which paralyze even the basic daily functioning of a person. When memory is encoded by fewer neurons it can be forgotten easily. As a result of this, treatments which increase the recruitment of a large number of neurons for encoding a memory help in preventing memory loss.

When an activity is practiced a lot, there are more chances of remembering it as more neurons are encoded for the action. It is usually considered that to make a memory stable, individual connections to a neuron have to be strengthened. However, the study suggests that the memory can be stored for a long period of time with an increase in the neurons which encode it.

Research Paper: Persistence of neuronal representations through time and damage in the hippocampus