Publisher Health

Healthy adult brains are endowed with a vast number of synapses, structures that relay signals across nerve cells to enable communications, information processing and storage throughout the nervous system. Apart from dynamic periods when the brain is learning new information or skills, the number of the “glutamatergic” synapses, the major type of synapses that neurons use to activate each other, largely remains constant in adults.
In brain disorders such as Alzheimer’s, these synaptic connections, which hold our precious memories, are known to break down too early and disappear. This synapse degeneration is thought to start long before the loss of memory and accelerate as diseases progress. The causes of synapse degeneration in neurodegenerative disorders has not been well understood, mainly because scientists have not yet unraveled the key mechanisms that normally hold together these tiny structures (an average of one micrometer in diameter) throughout our lifetime.
Neurobiologists at the University of California San Diego have now uncovered the long-sought-after mechanisms behind the maintenance of glutamatergic synapses. Based on this fundamental discovery, Division of Biological Sciences Postdoctoral Scholar Bo Feng, Professor Yimin Zou and their colleagues have identified the main components driving amyloid beta-associated synapse degeneration. Amyloid beta are peptides of 36-43 amino acids derived from the amyloid precursor protein (APP) and are the main component of amyloid plaques found in the brains of people with Alzheimer’s disease.
Despite tremendous efforts, drug discovery for Alzheimer’s disease has not been successful. So far, the main approaches have been to either reduce amyloid beta production or clear amyloid beta plaques. The new discovery from UC San Diego researchers, published in Science Advances on August 18, 2021, suggests an alternative approach further downstream: protect synapses by directly blocking the toxic actions of amyloid beta.
Glutamatergic synapses are highly polarized structures with a presynaptic part from one nerve cell and a postsynaptic part from another. This type of polarity ensures the proper direction of information flow. Zou’s lab had previously found that during brain development the highly polarized synaptic structures are assembled by components of the planar cell polarity (PCP) pathway: a powerful signaling pathway that polarizes cell-cell junctions along the tissue plane. Using super resolution microscopy, the researchers detected the precise location of these same PCP signaling components, called Celsr3, Frizzled3 and Vangl2, in the glutamatergic synapses in the adult brain. They then found that removing these components, essential for the initial assembly of synapses from adult neurons, can dramatically alter the number of synapses. These surprising discoveries suggest that the overall synapse number in a normal brain is maintained by a fine balance between Celsr3 (which stabilizes synapse) and Vangl2 (which disassembles synapses).
Curious about whether these components are involved in synapse degeneration, they tested whether amyloid beta, a key driver of synapse loss in Alzheimer’s disease, affects the function or interaction of these proteins. In a series of experiments, they showed that amyloid beta oligomers bind to Celsr3 and allow Vangl2 to more effectively disassemble synapses, likely by weakening the interactions between Celsr3 and Frizzled3.

A scientific achievement for researchers at Tel Aviv University: printing an entire active and viable glioblastoma tumor using a 3D printer. The 3D-bioprinted tumor includes a complex system of blood vessel-like tubes through which blood cells and drugs can flow, simulating a real tumor.
The study was led by Prof. Ronit Satchi-Fainaro, Sackler Faculty of Medicine and Sagol School of Neuroscience, Director of the Cancer Biology Research Center, Head of the Cancer Research and Nanomedicine Laboratory and Director of the Morris Kahn 3D-BioPrinting for Cancer Research Initiative, at Tel Aviv University. The new technology was developed by PhD student Lena Neufeld, together with other researchers at Prof. Satchi-Fainaro’s laboratory: Eilam Yeini, Noa Reisman, Yael Shtilerman, Dr. Dikla Ben-Shushan, Sabina Pozzi, Dr. Galia Tiram, Dr. Anat Eldar-Boock and Dr. Shiran Farber.
The 3D-bioprinted models are based on samples from patients, taken directly from operating rooms at the Tel Aviv Sourasky Medical Center. The new study’s results were published today in the journal Science Advances.
“Glioblastoma is the most lethal cancer of the central nervous system, accounting for most brain malignancies,” says Prof. Satchi-Fainaro. “In a previous study, we identified a protein called P-Selectin, produced when glioblastoma cancer cells encounter microglia — cells of the brain’s immune system. We found that this protein is responsible for a failure in the microglia, causing them to support rather than attack the deadly cancer cells, helping the cancer spread. However, we identified the protein in tumors removed during surgery, but not in glioblastoma cells grown on 2D plastic petri dishes in our lab. The reason is that cancer, like all tissues, behaves very differently on a plastic surface than it does in the human body. Approximately 90% of all experimental drugs fail at the clinical stage because the success achieved in the lab is not reproduced in patients.”
To address this problem, the research team led by Prof. Satchi-Fainaro and PhD student Lena Neufeld, recipient of the prestigious Dan David Fellowship, created the first 3D-bioprinted model of a glioblastoma tumor, which includes 3D cancer tissue surrounded by extracellular matrix, which communicates with its microenvironment via functional blood vessels.
“It’s not only the cancer cells,” explains Prof. Satchi-Fainaro. “It’s also the cells of the microenvironment in the brain; the astrocytes, microglia and blood vessels connected to a microfluidic system — namely a system enabling us to deliver substances like blood cells and drugs to the tumor replica. Each model is printed in a bioreactor we have designed in the lab, using a hydrogel sampled and reproduced from the extracellular matrix taken from the patient, thereby simulating the tissue itself. The physical and mechanical properties of the brain are different from those of other organs, like the skin, breast, or bone. Breast tissue consists mostly of fat, bone tissue is mostly calcium; each tissue has its own properties, which affect the behavior of cancer cells and how they respond to medications. Growing all types of cancer on identical plastic surfaces is not an optimal simulation of the clinical setting.”
After successfully printing the 3D tumor, Prof. Satchi-Fainaro and her colleagues demonstrated that unlike cancer cells growing on petri dishes, the 3D-bioprinted model has the potential to be effective for rapid, robust, and reproducible prediction of the most suitable treatment for a specific patient.
“We proved that our 3D model is better suited for prediction of treatment efficacy, target discovery and drug development in three different ways. First, we tested a substance that inhibited the protein we had recently discovered, P-Selectin, in glioblastoma cell cultures grown on 2D petri dishes, and found no difference in cell division and migration between the treated cells and the control cells which received no treatment. In contrast, in both animal models and in the 3D-bioprinted models, we were able to delay the growth and invasion of glioblastoma by blocking the P-Selectin protein. This experiment showed us why potentially effective drugs rarely reach the clinic simply because they fail tests in 2D models, and vice versa: why drugs considered a phenomenal success in the lab, ultimately fail in clinical trials. In addition, collaborating with the lab of Dr. Asaf Madi of the Department of Pathology at TAU’s Faculty of Medicine, we conducted genetic sequencing of the cancer cells grown in the 3D-bioprinted model, and compared them to both cancer cells grown on 2D plastic and cancer cells taken from patients. Thus, we demonstrated a much greater resemblance between the 3D-bioprinted tumors and patient-derived glioblastoma cells grown together with brain stromal cells in their natural environment. Through time, the cancer cells grown on plastic changed considerably, finally losing any resemblance to the cancer cells in the patient’s brain tumor sample. The third proof was obtained by measuring the tumor growth rate. Glioblastoma is an aggressive disease partially because it is unpredictable: when the heterogeneous cancer cells are injected separately into model animals, the cancer will remain dormant in some, while in others, an active tumor will develop rapidly. This makes sense because we, as humans, can die peacefully of old age without ever knowing we have harbored such dormant tumors. On the dish in the lab, however, all tumors grow at the same rate and spread in the same rate. In our 3D-bioprinted tumor, the heterogeneity is maintained and development is similar to the broad spectrum that we see in patients or animal models.”
According to Prof. Satchi-Fainaro, this innovative approach will also enable the development of new drugs, as well as discovery of new drug targets — at a much faster rate than today. Hopefully, in the future, this technology will facilitate personalized medicine for patients.
“If we take a sample from a patient’s tissue, together with its extracellular matrix, we can 3D-bioprint from this sample 100 tiny tumors and test many different drugs in various combinations to discover the optimal treatment for this specific tumor. Alternately, we can test numerous compounds on a 3D-bioprinted tumor and decide which is most promising for further development and investment as a potential drug. But perhaps the most exciting aspect is finding novel druggable target proteins and genes in cancer cells — a very difficult task when the tumor is inside the brain of a human patient or model animal. Our innovation gives us unprecedented access, with no time limits, to 3D tumors mimicking better the clinical scenario, enabling optimal investigation.”
The study was funded by the Morris Kahn Foundation, European Research Council (ERC), Israel Cancer Research Fund (ICRF), the Israel Cancer Association and Israel Science Foundation (ISF), and Check Point Software Technologies LTD.

For people with amputation who have prosthetic limbs, one of the greatest challenges is controlling the prosthesis so that it moves the same way a natural limb would. Most prosthetic limbs are controlled using electromyography, a way of recording electrical activity from the muscles, but this approach provides only limited control of the prosthesis.
Researchers at MIT’s Media Lab have now developed an alternative approach that they believe could offer much more precise control of prosthetic limbs. After inserting small magnetic beads into muscle tissue within the amputated residuum, they can precisely measure the length of a muscle as it contracts, and this feedback can be relayed to a bionic prosthesis within milliseconds.
In a new study appearing today in Science Robotics, the researchers tested their new strategy, called magnetomicrometry (MM), and showed that it can provide fast and accurate muscle measurements in animals. They hope to test the approach in people with amputation within the next few years.
“Our hope is that MM will replace electromyography as the dominant way to link the peripheral nervous system to bionic limbs. And we have that hope because of the high signal quality that we get from MM, and the fact that it’s minimally invasive and has a low regulatory hurdle and cost,” says Hugh Herr, a professor of media arts and sciences, head of the Biomechatronics group in the Media Lab, and the senior author of the paper.
Cameron Taylor, an MIT postdoc, is the lead author of the study. Other authors include MIT postdoc Shriya Srinivasan, MIT graduate student Seong Ho Yeon, Brown University professor of ecology and evolutionary biology Thomas Roberts, and Brown postdoc Mary Kate O’Donnell.
Precise measurements
With existing prosthetic devices, electrical measurements of a person’s muscles are obtained using electrodes that can be either attached to the surface of the skin or surgically implanted in the muscle. The latter procedure is highly invasive and costly, but provides somewhat more accurate measurements. However, in either case, electromyography (EMG) offers information only about muscles’ electrical activity, not their length or speed.

One of the most vaccinated societies, Israel now has one of the highest infection rates in the world, raising questions about the vaccine’s efficacy.JERUSALEM — Last spring, Israel’s remarkably swift vaccination campaign was seen as a global model. Coronavirus infections plummeted, an electronic pass allowed the vaccinated to attend indoor concerts and sporting events, and distancing rules and mask mandates were eventually scrapped.Israel offered the world a hopeful glimpse of the way out of the pandemic.No longer.A fourth wave of infections is rapidly approaching the levels of Israel’s worst days of the pandemic last winter. The daily rate of confirmed new virus cases has more than doubled in the last two weeks, making Israel a rising hot spot on the international charts.Restrictions on gatherings and commercial and entertainment venues were reinstated this week, and the government is considering a new lockdown.“I believe we are at war,” Israel’s coronavirus commissioner, Prof. Salman Zarka, told a parliamentary committee on Wednesday.Scientists are still assessing how Israel’s pandemic response plunged from shining example to cautionary tale, and the stunning reversal has provided a crucial test for Israel’s new prime minister, Naftali Bennett, who staked a claim for leadership partly on the strength of his manifesto, “How to Beat a Pandemic.”But some experts fear that Israel’s high rate of infections among early vaccine recipients may indicate a waning of the vaccine’s protections over time, a finding that contributed to a U.S. decision Wednesday that to begin offering booster shots to Americans widely starting next month.Waiting to receive a third dose of the vaccine last week in Jerusalem. More than a million Israelis have already received a booster shot.Ammar Awad/ReutersThe vaccine may be less effective at preventing infection with the highly contagious Delta variant, now the primary version of the virus in Israel. And the first cohort to be vaccinated was an older group whose immune systems may have been weaker to begin with.By June, Israelis, convinced the worst was over, had abandoned social distancing and other precautions.“Everyone went about the business of trying to put the memory of a very difficult year and a half behind them,” said Prof. Ran Balicer, chairman of an expert panel that advises the Israeli government on Covid response.“At that point in time,” he said, “the paradigm for many was that Israel is the most vaccinated country in the world, that vaccinated people rarely become infected, that even more rarely do they become severely ill and that basically, with very few precautions in place, the population was very close to herd immunity, all things considered. That was not a mistake.”The problem, he said, was that what was true for the original virus “did not necessarily hold true for future variants coupled with waning immunity.”The vast majority of Israel’s older population had received two doses of the Pfizer-BioNTech vaccine by the end of February, and by now about 78 percent of the population 12 and older are fully vaccinated.At a cinema in May in Jerusalem. By June, the government had lifted most antivirus restrictions.Abir Sultan/EPA, via ShutterstockThe vaccine is still believed to help prevent severe illness in those who do become infected, though some Israeli data suggests the possibility of an increased risk of severe disease among those who received early vaccinations. The number of deaths in Israel has climbed in the past month as the infection rate increased.Seeing infection levels dropping in the spring, and determined to reboot the economy, Israel retired its electronic pass system, eased travel bans and lifted all other restrictions. The last to go was the indoor mask mandate on June 15.Days earlier, however, a family had returned from a Greek vacation to the central city of Modiin, a middle class commuter hub between Tel Aviv and Jerusalem. More than 90 percent of its residents 12 and over are vaccinated, according to its mayor, Haim Bibas, making it one of Israel’s most vaccinated cities.But the family included a child too young to be vaccinated, and who should have spent at least 10 days in home quarantine pending a negative PCR test, according to the regulations at the time.Instead, the parents sent the child to school. Ultimately, about 80 students were infected with the Delta variant.“The child wasn’t to blame,” Mr. Bibas said, indirectly pointing a finger at the parents.A second outbreak occurred almost simultaneously in similar circumstances in a school in the north.Prime Minister Naftali Bennett, left, in Jerusalem last month, was slow to respond to the resurgent virus, favoring an approach that kept businesses operating at full capacity. Pool photo by Ronen ZvulunThe Delta variant has since taken over in Israel, and now mainly comes from within the country.Professor Balicer had warned in May that despite the early success, Israel’s pandemic was not over. There was the continuous risk of variants that could be more impervious to the vaccine. Out of a population of nine million, about a million eligible Israelis have so far opted not to get vaccinated at all. And among the fully inoculated, Israeli scientists have found growing evidence of waning immunity, particularly among the older population who were vaccinated first.Data published by Israel’s Ministry of Health in late July suggested that the Pfizer shot was just 39 percent effective against preventing infection in the country in late June and early July, compared with 95 percent from January to early April. In both periods, however, the shot was more than 90 percent effective in preventing severe disease.Experts warn that these early assessments have not been scientifically proven: The small numbers of cases involved, Israel’s testing policies and a host of other biases could have skewed the results.Still, as summer approached, infections began to spiral. School was out, families crowded local hotels and up to 40,000 people a day were flying abroad, even as the Delta variant was rampaging across the globe. After many days of zero Covid deaths in June, at least 230 Israelis have died so far this month.Israelis and vaccinated tourists arriving in Tel Aviv airport in May. As infection levels dropped in the spring Israel eased travel restrictions.Jack Guez/Agence France-Presse — Getty ImagesUnlike previous epicenters of infection in Israel’s crowded, less-vaccinated ultra-Orthodox communities, this scourge primarily took hold in well-vaccinated, middle-class suburbs..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}Some experts have accused the new government of having been slow to respond.The resurgence of the contagion coincided with the swearing in of Mr. Bennett’s government in mid-June. After three Israeli lockdowns, Mr. Bennett came in with a new approach, determining that the country had to live with the virus and keep business operating at full capacity. He called the policy “soft suppression.”An indoor mask mandate was reinstated on June 25, but compliance was lax. Alarmed medical experts began to urge stricter measures, including curbs on all gatherings. The government advisory panel called twice — in July and again on Aug. 1 — for the immediate reinstatement of the electronic Green Pass system.“It was only in the last two weeks that a sense of urgency returned,” said Prof. Nadav Davidovitch, a public health expert and a member of the advisory panel. “What we are doing now, we needed to do in July.”But after the premature euphoria of the spring, virus fatigue has made returning to strict antivirus protocols difficult.“It’s a matter of discipline,” said Prof. Galia Rahav, the head of the Infectious Disease Unit and Laboratories at the Sheba Medical Center near Tel Aviv. “People are sick of masks. They want to live.”Officials worry that many Israelis are still oblivious to the rising danger.“The Israeli public has not yet absorbed that we are in a fourth, significant wave,” said Tomer Lotan, director general of the Ministry of Public Security, which is responsible for enforcement. “We are still in routine mode, with the feeling that we are vaccinated. It’s hard to make the switch in public discourse and say, ‘Listen, we are in a catastrophe.’”Playing in a water fountain this month in Jerusalem. “People are sick of masks,” one expert said. “They want to live.”Abir Sultan/EPA, via ShutterstockIsrael is now pinning its hopes on booster shots. Beginning with those 60 and older, and quickly expanding the drive to those 50 and above, more than a million citizens have already received a third dose this month. Israeli researchers say there are preliminary signs that new infections among older vaccinated people may have begun to drop.A preliminary study released Wednesday by Maccabi, an Israeli health-care provider, found that a booster shot of the Pfizer vaccine provided 86 percent effectiveness against infection in people aged over 60, a week or more after receiving the third dose.A global debate is raging over boosters. The Biden administration announced Wednesday that Americans who received the Pfizer-BioNTech and Moderna vaccines would be able to obtain booster shots eight months after receiving their second doses.But the World Health Organization contends that available vaccines would be better used to inoculate high-risk people in poor nations where few have gotten the shots and where new variants could emerge.Most Palestinians in the West Bank and Gaza remain unvaccinated after Palestinian officials rejected a vaccine-exchange deal with Israel in June.Professor Davidovitch, the Israeli public health expert, got a third shot. But he is now convinced of the necessity of a multilayered strategy, including mask wearing, limiting access to public venues to the vaccinated or those who have recovered from the virus, and measures to strengthen the health care system.“The vaccinations were supposed to solve everything,” he said. “We now understand that the vaccines are not enough.”

Eating a hot dog could cost you 36 minutes of healthy life, while choosing to eat a serving of nuts instead could help you gain 26 minutes of extra healthy life, according to a University of Michigan study.
The study, published in the journal Nature Food, evaluated more than 5,800 foods, ranking them by their nutritional disease burden to humans and their impact on the environment. It found that substituting 10% of daily caloric intake from beef and processed meats for a mix of fruits, vegetables, nuts, legumes and select seafood could reduce your dietary carbon footprint by one-third and allow people to gain 48 minutes of healthy minutes per day.
“Generally, dietary recommendations lack specific and actionable direction to motivate people to change their behavior, and rarely do dietary recommendations address environmental impacts,” said Katerina Stylianou, who did the research as a doctoral candidate and postdoctoral fellow in the the Department of Environmental Health Sciences at U-M’s School of Public Health. She currently works as the Director of Public Health Information and Data Strategy at the Detroit Health Department.
This work is based on a new epidemiology-based nutritional index, the Health Nutritional Index, which the investigators developed in collaboration with nutritionist Victor Fulgoni III from Nutrition Impact LLC. HENI calculates the net beneficial or detrimental health burden in minutes of healthy life associated with a serving of food consumed.
Calculating impact on human health
The index is an adaptation of the Global Burden of Disease in which disease mortality and morbidity are associated with a single food choice of an individual. For HENI, researchers used 15 dietary risk factors and disease burden estimates from the GBD and combined them with the nutrition profiles of foods consumed in the United States, based on the What We Eat in America database of the National Health and Nutrition Examination Survey. Foods with positive scores add healthy minutes of life, while foods with negative scores are associated with health outcomes that can be detrimental for human health.

Research led by a Wayne State University Department of Mathematics professor is aiding researchers in Wayne State’s Department of Psychiatry and Behavioral Neurosciences in analyzing fMRI data. fMRI is the preeminent class of signals collected from the brain in vivo and is irreplaceable in the study of brain dysfunction in many medical fields, including psychiatry, neurology and pediatrics.
Andrew Salch, Ph.D., associate professor of mathematics in Wayne State’s College of Liberal Arts and Sciences, is leading the multidisciplinary team that is investigating how concepts of topological data analysis, a subfield of mathematics, can be applied to recovering “hidden” structure in fMRI data.
“We hypothesized that aspects of the fMRI signal are not easily discoverable using many of the standard tools used for fMRI data analysis, which strategically reduce the number of dimensions in the data to be considered. Consequently, these aspects might be uncovered using concepts from the mathematical field of topological data analysis, also called TDA, which is intended for use on high-dimensional data sets,” said Salch. “The high dimensionality that characterizes fMRI data includes the three dimensions of space — that is, where in the brain the signal is being acquired — time — or how the signal varies as brain states change in time — and signal intensity — or how the strength of the fMRI signal changes in response to the task. When related to task-induced changes, the results reflect biologically meaningful aspects of brain function and dysfunction. This is a unique collaborative work focused on the complexities of both TDA and fMRI respectively, show how TDA can be applied to real fMRI data collected, and provide open access computational software we have developed for implementing the analyses.”
The research article, “From mathematics to medicine: A practical primer on topological data analysis and the development of related analytic tools for the functional discovery of latent structure in fMRI data,” appears in the Aug. 12 issue of PLOS ONE.
In it, the team used TDA to discover data structures in the anterior cingulate cortex, a critical control region in the brain. These structures — called non-contractible loops in TDA — appeared in specific conditions of the experiment, and were not identified using conventional techniques for fMRI analyses.
“We expect this work to become a citation classic,” said Vaibhav Diwadkar, Ph.D., professor of psychiatry and behavioral neurosciences and research collaborator. “Instead of merely applying TDA to fMRI, we provide a lucid argument for why medical researchers who use fMRI should consider using TDA, and why topologists should turn their attention to the study of complex fMRI data. Moreover, this important work provides readers with empirical demonstrations of such applications, and we provide potential users with the tools we used so they can in turn apply it to their own data.”
“Our ongoing research utilizing TDA with fMRI will provide a unique and complementary method for assessing brain function, and will give medical researchers greater flexibility in tackling complex properties in their data,” said Salch. “In particular, our work will help fMRI researchers become aware of the significant power of TDA that is designed to address complexity in data, and will enhance the value of using fMRI in neuroscience and medicine.”
In addition to Salch and Diwadkar, co-authors on the paper include Adam Regalski, Wayne State mathematics graduate student; Hassan Abdallah, Wayne State mathematics department alumni and current graduate student at the University of Michigan; and Michael Catanzaro, assistant professor of mathematics at Iowa State University and Wayne State mathematics department alumni.
This work is supported by the National Institutes of Health (MH111177 and MH059299), the Jack Dorsey Endowment, the Cohen Neuroscience Endowment, and the Lycaki-Young Funds from the State of Michigan.

Eating fructose appears to alter cells in the digestive tract in a way that enables it to take in more nutrients, according to a preclinical study from investigators at Weill Cornell Medicine and NewYork-Presbyterian. These changes could help to explain the well-known link between rising fructose consumption around the world and increased rates of obesity and certain cancers.
The research, published August 18 in Nature, focused on the effect of a high-fructose diet on villi, the thin, hairlike structures that line the inside of the small intestine. Villi expand the surface area of the gut and help the body to absorb nutrients, including dietary fats, from food as it passes through the digestive tract. The study found that mice that were fed diets that included fructose had villi that were 25 percent to 40 percent longer than those of mice that were not fed fructose. Additionally, the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals.
“Fructose is structurally different from other sugars like glucose, and it gets metabolized differently,” said senior author Dr. Marcus DaSilva Goncalves, the Ralph L. Nachman Research Scholar, an assistant professor of medicine in the Division of Endocrinology, Diabetes and Metabolism and an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Our research has found that fructose’s primary metabolite promotes the elongation of villi and supports intestinal tumor growth.”
The investigators didn’t plan to study villi. Previous research from the team, published in 2019, found that dietary fructose could increase tumor size in mouse models of colorectal cancer, and that blocking fructose metabolism could prevent that from happening. Reasoning that fructose might also promote hyperplasia, or accelerated growth, of the small intestine, the researchers examined tissues from mice treated with fructose or a control diet under the microscope.
The observation that the mice on the high-fructose diet had increased villi length, which was made by first author Samuel Taylor, a Tri-Institutional M.D.-Ph.D. Program student in Dr. Goncalves’ lab, was a complete surprise. And once he made the discovery, he and Dr. Goncalves set out to learn more.
After observing that the villi were longer, the team wanted to determine whether those villi were functioning differently. So they put mice into three groups: a normal low-fat diet, a high-fat diet, and a high-fat diet with added fructose. Not only did the mice in the third group develop longer villi, but they became more obese than the mice receiving the high-fat diet without fructose.
The researchers took a closer look at the changes in metabolism and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels. This metabolite interacted with a glucose-metabolizing enzyme called pyruvate kinase, to alter cell metabolism and promote villus survival and elongation. When pyruvate kinase or the enzyme that makes fructose-1-phospate were removed, fructose had no effect on villus length. Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth.
According to Taylor, the observations in mice make sense from an evolutionary perspective. “In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,” he said. “Eating a lot of fructose may help these animals to absorb and convert more nutrients to fat, which they need to get through the winter.”
Dr. Goncalves added that humans did not evolve to eat what they eat now. “Fructose is nearly ubiquitous in modern diets, whether it comes from high-fructose corn syrup, table sugar, or from natural foods like fruit,” he said. “Fructose itself is not harmful. It’s a problem of overconsumption. Our bodies were not designed to eat as much of it as we do.”
Future research will aim to confirm that the findings in mice translate to humans. “There are already drugs in clinical trials for other purposes that target the enzyme responsible for producing fructose-1-phosphate,” said Dr. Goncalves, who is also a member of the Sandra and Edward Meyer Cancer Center. “We’re hoping to find a way to repurpose them to shrink the villi, reduce fat absorption, and possibly slow tumor growth.”
Dr. Marcus DaSilva Goncalves is a paid consultant and shareholder of Faeth Therapeutics which is developing therapies for cancer. Dr. Goncalves has received speaking and/or consulting fees from Pfizer, Novartis, Petra Pharmaceuticals and TruMacro Nutrition. The laboratory of Dr. Goncalves has received financial support from Pfizer.

Wearable health technologies are vastly popular with people wanting to improve their physical and mental health. Everything from exercise, sleep patterns, calories consumed and heart rhythms can be tracked by a wearable device.
But timely and accurate data is also especially valuable for doctors treating patients with complicated health conditions using virtual care.
A new study from the Southern Medical Program (SMP), based at UBC Okanagan, has examined the use of wearable health technology and telehealth to treat patients with Parkinson’s disease.
Dr. Daryl Wile, a movement disorder specialist and SMP clinical assistant professor, routinely uses telehealth to connect with Parkinson’s patients across the vast and rugged landscape of BC’s Interior.
“Even prior to the pandemic, telehealth helped deliver specialized care to patients living in remote and rural settings,” says Wile, a clinical investigator with the Centre for Chronic Disease Prevention and Management. “But with the complex nature of Parkinson’s, we wanted to enhance these appointments to better understand how movements vary throughout a patient’s entire day.”
To add a new layer of health information, Wile and the research team added wearable technology to the equation.
“We recruited Parkinson’s patients with either tremors or involuntary movements,” says Joshua Yoneda, SMP student and co-author of the study. “We then divided them into two groups — some using telehealth and device-based health tracking and others attending traditional face-to-face appointments.”
The telehealth group wore wearable devices to track their movements, involuntary or not, throughout waking hours. The reported data was then reviewed during telehealth appointments to identify peak times patients experienced Parkinson’s symptoms.
“With the integration of accurate and reliable data from wearable devices, we were able to tailor a patient’s medication to better manage their symptoms throughout the day,” adds Wile.
As part of the study, patients were asked a series of questions from the standardized Parkinson Disease Quality of Life Index. Both study groups were assessed at intervals of six weeks, three months and six months.
Overall, the patients using the wearable devices reported positive experiences and health outcomes in combination with telehealth appointments to access specialized care.
“There’s definitely a strong case to leverage multiple technologies to improve a patient’s quality of life and limit the added stress and cost associated with travel,” says Yoneda.
Story Source:
Materials provided by University of British Columbia Okanagan campus. Note: Content may be edited for style and length.

Video images capture for the first time in live animals the inexorable spread of the COVID-19 virus, tracking the infection as it moved from the noses of mice to the lungs and other organs over the course of six days, in a new study led by researchers at Yale and Université de Montréal.
While the images record the sometimes deadly march of SARS-CoV-2, the virus that causes COVID-19, they also show how the introduction of antibodies collected from humans who recovered from the virus can prevent or treat infection.
However, the research also revealed that antibodies lacking the ability to recruit killer immune system cells are less effective at combating infection.
The study, published online Aug. 18 in preproof form in the journal Immunity, was led by Priti Kumar, Pradeep Uchil, and Walther Mothes, all from Yale School of Medicine, as well as Andrés Finzi from Université de Montréal.
“For the first time, we were able to visualize the spread of the SARS-CoV-2 in a living animal in real time, and importantly, the sites at which antibodies need to exert effects to halt progression of infection,” said Kumar, associate professor of infectious diseases at Yale School of Medicine and a co-corresponding author of the paper.
For the study, co-lead authors Irfan Ullah, a Yale postdoctoral associate, and Jérémie Prévost, from Montreal, used bioluminescent tagging and advanced microscopy to track the spread of the virus down to the level of single cells. In mice, the virus took a route that has become familiar to doctors treating human patients, with high viral loads first appearing in nasal passages and then travelling quickly to lungs and eventually other organs. The mice eventually died when virus reached the brain.
The researchers then used plasma from humans who had recovered from COVID-19 to treat some of the infected mice, which halted the spread of the virus even when administered as late as three days after infection. When these antibodies were administered prior to infection with the virus, researchers found, they prevented infection altogether.
“The live reporting of virus spread by imaging can be harnessed to rapidly discern whether treatments will work or not in as little as three to five days, a crucial time-saving feature to develop countermeasures for current and future pandemics” said Uchil, a research scientist in Mothes’ lab in the Department of Microbial Pathogenesis at Yale.
Researchers found that not all antibodies worked equally well, however. Antibodies have two main roles. Neutralizing antibodies bind to and prevent viruses from entering cells. Then, a second part of the antibody exhibits what are known as “effector” functions, which are necessary to signal the immune system to attack and kill cells that are infected.
“Antibodies are polyfunctional molecules with several properties,” Finzi said. “In this study we show that their capacity to ‘call for help’ from other cells in the immune system and eliminate infected cells is required to provide optimal protection.”
Added Kumar: “We used to think neutralizing the virus was enough to prevent infection, but antibodies have to be present at the right time in the right place in the body and in right amount. Without the effector function, the neutralizing activity alone is not as effective.”
Other collaborators included Craig Wilen from Yale University, Mark Ladinsky and Pamela Bjorkman from California Institute of Technology, Leonidas Stamatatos and Andrew McGuire from Fred Hutchinson Cancer Research Center, and Marzena Pazgier from Uniformed Services University of the Health Sciences.
Story Source:
Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

A team of researchers led by bioengineers at the Georgia Institute of Technology is expanding the precision and ability of a revolutionary immunotherapy that is already transforming oncology. CAR T-Cell therapy has been hailed by patients, clinical-researchers, investors, and the media as a viable cure for some cancers.
CAR T-Cell therapy involves engineering a patient’s T-cells, a type of white blood cell, in a lab. Then a chimeric antigen receptor (CAR) is added, and these customized immune cells are returned to the patient’s body, where they seek and destroy cancer cells. That’s how it works, when it works.
It’s a new, evolving, and booming area of immunotherapy, with more than 500 clinical trials analyzing CAR T-cells for cancer treatment going on right now around the world.
“These therapies have proven to be remarkably effective for patients with liquid tumors — so, tumors that are circulating in the blood, such as leukemia,” said Gabe Kwong, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “Unfortunately, for solid tumors — sarcomas, carcinomas — they don’t work well. There are many different reasons why. One huge problem is that the CAR T-cells are immunosuppressed by the tumor microenvironment.”
Kwong and his collaborators are changing the environment and making some cell modifications of their own to enhance the way CAR T-cells fight cancer. They’ve added a genetic on-off switch to the cells and a developed a remote-control system that sends the modified T-cells on a precision invasion of the tumor microenvironment, where they kill the tumor and prevent a relapse. And they explain it all in a study published recently in the journal Nature Biomedical Engineering.
The latest study builds on the lab’s body of work exploring remotely controlled cell therapies, in which the researchers can precisely target tumors, wherever they are in the body, with a local deposition of heat. “And this heat basically activates the CAR T-cells inside the tumors, overcoming the problems of immunosuppression,” said Kwong.